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H a r v a r d U n i v e r s i t y
Division of the Life Sciences
16 Divinity Avenue
Cambridge, Massachusetts 02138
November, 2010
Dear Harvard Community,
I would like to thank the editors for inviting me to introduce this issue of THURJ.
Those of us who are involved in science education at Harvard recognize the tremendous value
of an undergraduate research experience. Harvard students, too, are enthusiastic about this aspect
of their college career. Indeed, many of them choose to come here because they realize that they
will be encouraged to become a part of Harvard’s extraordinarily rich and diverse scientific research
community. Through participation in basic research, students learn how to frame appropriate
questions, design experiments, and analyze new data. Some of these concepts may be learned in the
classroom, but they are fostered and refined by the opportunity to work in depth on an independent
research project in the laboratory or the field.
But beyond mastering the necessary skills and techniques, designing experiments, and analyzing
data; learning to communicate research questions and results to both peers and non-scientists is a
crucial step toward becoming a member of the community of science scholars. Students should take
advantage of every chance to present their research by, for example, giving group meeting talks to lab
mates, presenting posters for HURS or submitting papers for publication. As a journal dedicated to
undergraduate research, THURJ offers an excellent opportunity for students to prepare manuscripts
on their projects. One has only to look at previous issues of THURJ to see the breadth of interesting
and well-written articles by students. I congratulate everyone involved with THURJ for producing
this outstanding journal and providing our students with such a professional publication in which to
showcase their work.
Sincerely,
Ann Georgi
Undergraduate Research Advisor in Life Sciences

Life Sciences Education Office
111234$562"57 !"
LETTERS !"#$%&'(')**$&'+','-.##'+/0/
The Harvard Undergraduate Research Journal
November, 2010
Dear Harvard Community,
We proudly present the Fall 2010 issue of The Harvard Undergraduate Research Journal. Every
semester, these pages are at once a celebration of the astonishing intellectual inquiry pursued by
Harvard undergraduates and an effort to seriously engage members of the Harvard community,
especially the College, with the research endeavors happening around them.
This semester is no different. Our staffers have once again explored a diverse spectrum of new
scientific inroads from the new methodological opportunities found at the Institute of Quantitative
Social Sciences to a large scale study revealing common mutations across different cancer types. We
are honored to showcase original undergraduate research spanning the natural to the biological to
the social sciences. Our prize-winning article by Melissa Deas presents a nuanced investigation of
gentrification in terms of the polyphonic array of community members in Hyde Jackson Square who
interpret, contest, and support its renaming to Boston’s Latin Quarter. In addition, reflecting our
mission to share undergraduate research with the undergraduate community, this issue provides
research article summaries that discuss the paper and its significance in an accessible and intriguing
way.
We hope that this sixth issue of THURJ is as interesting and thrilling to read for you as it was for
us and our authors to produce. We thank our student and faculty reviewers, our designers and staff
writers, and our Social and Public Relations and Business board members who each play an integral
role in fulfilling our mission. THURJ’s passion and hard work every semester are aimed toward
sharing, as best we can, the significance and diversity of research in the undergraduate experience. We
are grateful to those who, in sharing this goal, continue to support us, especially FAS Dean of Science
Jeremy Bloxham, SEAS Dean Cherry Murray, Professor Richard Losick, Professor Steven Freedman,
Provost Steven Hyman, FAS Dean Michael Smith, Dean Evelynn Hammonds, and Harvard College.
Please enjoy.
Sincerely,
John Mei Grace Cho

Co-Editor-in-Chief Co-Editor-in-Chief
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Contents
Research
72 Article summaries
75 Surface morphology and electrical properties

of GaN layers and AlGaN/GaN high electron
mobility transistor (HEMT) structures grown by
molecular beam epitaxy
82 123
Michael Lindeborg ‘14 103 The role of the informal sector in
equitable water distribution: A case study of the
82 Who has the right to define place: tanker market in Ayn al-Basha, Jordan
Authenticity in Boston’s Latin Quarter from Sarah Hinkfuss ‘10
the perspective of white gentrifiers and old
timers 116 Minimum assignment problem
Melissa Deas ‘10 Olga Zverovich ‘10
123 Development of an automated head-fixed

92 Structure-function analysis of newly- preparation to study the neuronal mechanisms
identified adamantylacetamide and of motor learning in rodents
adamantanecarboxamide inhibitors of Ebola and Kate Xie ‘10
Lassa fever virus infection
Huy Nguyen ‘10 133 Abstracts of online articles
Features
134 “A team sport”: Collaboration at the Institute
for Qualitative Social Sciences
Jen Gong ‘12
137 142
137 Light, genes, and action: Understanding the
function of neural circuits 139 What underlies cancer: A collaborative study
Jung Soo Lee ‘12 unearths common mutations
Patrick Snodgrass ‘13
142 Check it off: A review of Atul Gawande’s

latest book
Alissa D’Gama ‘11
144 From crude oil to olive oil

134 139 Cherry A. Murray, Dean of HSEAS
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Managing Editor of Content Executive Board

Design Chair
Jen Gong ‘12 Co-Editors-in-Chief Amanda Lu ‘13
John Mei ‘12 and Grace Cho ‘12
Managing Editor of Peer Review and
Manager for Social and Public Relations
Submissions Business Manager Janet Song ‘13
Will Sun ‘13 Varun Bansal ‘13
Boards Faculty Advisory Board

Business Alán Aspuru-Guzik, Ph.D David Jeruzalmi, Ph.D
Assistant Professor of Chemistry and Chemical Associate Professor of Molecular and Cellular
Director of Operations: Peter Zhang ’13 Biology Biology
Director of Advertising: Neal Wu ‘14 Paul Bamberg, Ph.D Efthimios Kaxiras, Ph.D
Director of Marketing and Circulation: Senior Lecturer on Mathematics Gordon McKay Professor of Applied Physics
Yvette Leung ‘13 Michael Brenner, Ph.D and Professor of Physics
Glover Professor of Applied Mathematics and George Lauder, Ph.D
Alison Liou ‘14 Applied Physics Professor of Biology and Alexander Agassiz
Grace Qi ‘14 Myron Essex, D.V.M., Ph.D Professor of Zoology
Nathan Geonwoo Kim ‘13 Mary Woodard Lasker Professor of Health Richard Losick, Ph.D
Jennifer Sun ‘14 Sciences in the Faculty of Public Health Maria Moors Cabot Professor of Biology
John Sheridan ‘13 Brian Farrell, Ph.D L. Mahadevan, Ph.D
Kathy Wang ‘14 Professor of Biology Lola England Professor of Applied
Jeffrey Flier, M.D. Mathematics
Kyle Kost ‘14
Nicholas Moore ‘14 Dean, Harvard Medical School, and George C. David Mooney, Ph.D
Reisman Professor of Medicine Gordon McKay Professor of Bioengineering
Nolan Kamitaki ‘14
Nicole Francis, Ph.D Hongkun Park, Ph.D
Namhun Scott Kim ‘14 Associate Professor of Molecular and Cellular Professor of Chemistry and of Physics
Robert Powers ‘14 Biology Steven Pinker, Ph.D
Jonathan Zhou ‘14 Steven Freedman, M.D., Ph.D Johnstone Family Professor of Psychology
Zijian Wu ‘14 Associate Professor of Medicine Tobias Ritter, Ph.D
Robin Greenwood, Ph.D Assistant Professor of Chemistry and Chemical
Content Associate Professor of Business Administration Biology
Associate Managing Editors: Guido Guidotti, Ph.D Eugene Shakhnovich, Ph.D
Alissa D’Gama ‘11 Higgins Professor of Biochemistry Professor of Chemistry and Chemical Biology
Jung Soo (Tom) Lee ‘12 David Haig, Ph.D Irwin Shapiro, Ph.D
Michelle Wang ‘14 George Putnam Professor of Organismic and Timken University Professor
Evolutionary Biology Stuart M. Shieber, Ph.D
Ina Chen ‘14 Marc Hauser, Ph.D James O. Welch, Jr. and Virginia B. Welch
Professor of Psychology Professor of Computer Science
Logan Chestnut ‘14
Dudley Herschbach, Ph.D Zhigang Suo, Ph.D
Jonathan D’Gama ‘14 Frank B. Baird Jr. Professor of Science Allen E. and Marilyn M. Puckett Professor of
Nan Du ‘12 John Hutchinson, Ph.D Mechanics and Materials
Kyle Green ‘14 Abbott and James Lawrence Professor of David Weitz, Ph.D
Yvette Leung ‘14 Engineering and Gordon McKay Professor of Mallinckrodt Professor of Physics and of
Jenny Lu ‘14 Applied Mechanics Applied Physics
Saima Mir ‘14
Saraf Nawar ‘14
Meewon Park ‘14
Grace Qi ‘14
Faculty Reviewers
Patrick Snodgrass ‘13 Martin Hirsch Benito Munoz
Professor in the Department of Immunology Director of Medicinal Chemistry
Anji Tang ‘13
and Infectious Diseases David Parkes
Kathy Wang ‘14
Evelyn Hu Gordon McKay Professor of Computer Science
Jonathan Zhou ‘14 Gordon McKay Professor of Applied Physics Ann Owens
Andrew Zhou ‘14 and Electrical Engineering Graduate Student in Sociology and Social
Peer Review and Submissions Guido Imbens Policy
Associate Editors: Professor of Economics Naoshige Uchida
Nathan Kim ‘13 Efthimios Kaxiras Assistant Professor of Molecular and Cellular
John Hasbrouck Van Vleck Professor of Pure Biology
Patrick Snodgrass ‘13
and Applied Physics Brandon Van Dyck
Fiona Wood ‘13
Robert Kirshner Graduate Student in Government
Helen Yang ‘11 Clowes Professor of Science Bob Westervelt
Jessica Zeng ‘12 Steven Lawry Mallinckrodt Professor of Applied Physics &
Senior Research Fellow Physics and Professor of Physics
Marc Lipsitch
Professor of Epidemiology
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Copy Editors: Caroline Huang ‘13 Julie Chang ‘14

Ioana Florea ‘14 Edward Kogan ‘12 Abhishek Chintapalli ‘14
Yvette Leung ‘14 Alex Mays ‘12 Jung Soo (Tom) Lee ‘12
Allen Shih ‘13 Vikram Nathan ‘13 Shimwoo Lee ‘13
Sarvagna Patel ‘13 Xinrui Zhang ‘14
Jacob Cedarbaum ‘12 Jeanine Sinanan-Singh ‘13
Andrew Chen ‘12 Amy Tai ‘13 Social and Public Relations
Doris Chen ‘13 Akachimere Uzosike ‘13 Associate Manager: Preya Shah ‘13
Sway Chen ‘12 Katherine Xue ‘13 Caroline Huang ‘13
Justine Cheng ‘13 Rohini Shivamoggi ‘13
Ben Dobkin ‘12 Design Jeanine Sinanan-Singh ‘13
Meng Xiao He ‘11 Associate Chair: Ritchell van Dams ‘11 Jung Soo (Tom) Lee ‘12
Johnny Hu ‘11 Casey Alcantar ‘13 Shannon Purcell ‘12
Corrections
The table of contents on our last issue incorrectly stated that Stephanie Mok ‘09 was the author of “Searching for Dark
Matter Beyond the WMAP Haze.” The author is Lauren Weiss ‘10.
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Contact About Us
General: contact@thurj.org
The Harvard Undergraduate Research Journal (THURJ) showcases
Advertising: advertising@thurj.org
peer-reviewed undergraduate student research from all science and
Subscribing: subscriptions@thurj.org
quantitative social science disciplines. As a biannual publication,
Submissions: submissions@thurj.org THURJ familiarizes students with the process of manuscript
Website: http://www.thurj.org submission and evaluation. Moreover, it provides a comprehensive
forum for scientific discourse on the cutting-edge research that impacts
our world today.
Copyright 2010 The Harvard At its core, THURJ allows students to gain insight into the peer
Undergraduate Research Journal.
review process, which is central to modern scientific inquiry. All
THURJ manuscripts are rigorously reviewed by the Peer Review Board
No material appearing in this publication (consisting of Harvard undergraduates), and the top manuscripts
may be reproduced without written that they select are further reviewed by Harvard graduate students,
permission of the publisher, with the
exception of the rights of photographs post-doctoral fellows, and professors. This process not only stimulates
which may only be granted by the faculty-student collaboration and provides students with valuable
photographer. The opinions expressed feedback on their research, but also promotes collaboration between
in this magazine are those of the
contributors and are not necessarily
the College and Harvard’s many graduate and professional schools. In
shared by the editors. All editorial rights addition to publishing original student research papers, THURJ is also
are reserved. an important medium for keeping the Harvard community updated on
science research-related news and developments.
About the Cover

The Hyde-Jackson Square mural is part of the newly proposed Boston Latin Quarter, a neighborhood
undergoing gentrification. “Who has the right to define place: Authenticity in Boston’s Latin Quarter from the
perspective of white gentrifiers and Latino Old Timers” by Melissa Deas ‘10 examines the neighborhood and
its shifting cultural and economic identity.
Photo credit: Melissa Deas
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SUMMARIES Volume 3 Issue 2 | Fall 2010
Surface morphology and electrical properties of suitable for use especially in electronic devices utilizing microwave or
radio frequencies [3].
GaN layers and AlGaN/GaN high electron mobility This paper first observes the growth of gallium nitride crystals
transistor (HEMT) structures grown by molecular through a process called molecular beam epitaxy, in which the gallium
beam epitaxy by Michael Lindeborg p. 75 is heated until it sublimates into a gas and is then reacted with nitrogen
to slowly produce a thin-film crystal onto a substrate. The growth
Gallium nitride is a semiconductor that is used in a broad range experiments in this study were conducted at higher temperatures than
of electronic and optoelectronic devices, from cell phones, radar, and those previously conducted. By examining features such as surface
satellite GPS systems to lasers [1]. It is typically applied in electronics roughness and electron mobility as a function of different growth
as part of aluminum-gallium-nitride/gallium-nitride (AlGaN/GaN) high conditions such as the flow of the gallium (called Ga-flux) and the
electron mobility transistors (HEMT). Although currently high electron temperature of the substrate, this study adds further characterization
mobility transistors are made more commonly with materials such as of the growth of Gallium Nitride semiconductor crystals at a higher
gallium arsenide [2], AlGaN/GaN has shown to be very promising in temperature. The study also characterizes various properties of
producing better HEMTs. Among its advantages, AlGaN/GaN HEMTs aluminum-gallium-nitride/gallium-nitride (AlGaN/GaN) high electron
can endure high voltage without breakdown, which greatly reduces mobility transistors (HEMT), which can ultimately pave the way for the
power loss [1]. This ability to withstand high voltage in addition to its production of higher quality and more effective HEMTs. —Jenny Lu ‘14
high electron mobility, or low resistivity, makes this semiconductor very
References:
1. Fujitsu Laboratories Ltd. “Fujitsu Develops World’s First
Gallium-Nitride HEMT for Power Supply.” 24 June 2009.
<http://www.fujitsu.com/global/news/pr/archives/
month/2009/20090624-01.html>
2. “HEMT, High electron mobility transistor.” Radio-
Electronics.com. Ed. Ian Poole. Adrio Communications
Ltd. <http://www.radio-electronics.com/info/data/
Illustration by Julie Chang
semicond/fet-field-effect-transistor/hemt-phemt-
transistor.php>
3. Mishra, U.K., Parikh, P., Yi-Feng Wu. “AlGaN/
GaN HEMTs-an overview of device operation and
applications,” Proceedings of the IEEE. 90.6(2002): 1022-
1031.
Who Has the Right to Define Place: Authenticity

in Boston’s Latin Quarter from the Perspective of
White Gentrifiers and Latino Old Timers by Melissa
Deas p. 82
A place is much more than its name. To the unseeing tourist, the
restaurants, shops, and parks of the town color the name on a map.
To the resident of many years, it is the unbreakable history of culture
and community that forever paint the meaning of a place. The recent
debate over the renaming of Hyde Jackson Square to Boston’s Latin
Quarter provokes issues of white authenticity, gentrification, and Latino
identity of culture and history. For a community whose ethnic dynamics
are still changing, the name runs the risk of being a misnomer.
This ethnographic study analyzes the renaming of a community
and the perspectives of white gentrifiers and Latinos of the community
to understand the issue of who retains the right to define a place
socially and culturally shaped by history and restructured by the new
generation. The questions raised in this local area reflect a larger clash
of race and class prevalent in many multiracial urban neighborhoods
throughout America. Further understanding of such social dynamics
as in the case examined in this paper may lead to ways of addressing
the tensions caused by our ubiquitous, contending cultural and class Illustration by Julie Chang
forces. —Saima Mir ‘14
72 The Harvard Undergraduate Research Journal

Volume 3 Issue 2 | Fall 2010 SUMMARIES
Structure-Function Analysis of Newly- Ebola virus, EBOV, is a virus that causes serious hemorrhagic fever in
the body. Ebola fever is devastating: according to the National Institutes
Identified Adamantylacetamide and of Health [1], its mortality rate can be as high as 90%. Late stage patients
Adamantanecarboxamide Inhibitors of Ebola and with Ebola suffer from extensive bleeding from the body. The cause of
Lassa Fever Virus Infection by Huy Nguyen p. 92 death is usually shock, which is the lack of proper blood flow [1]. There
is currently no vaccine or drug in the market to treat Ebola hemorrhagic
fever patients. Moreover, Ebola cases are concentrated in Africa [2],
where the lack of good healthcare can make therapy and containment
difficult.
This study investigates two compounds: Compound 3.0 and
Compound 3.3. Compound 3.0 (an adamantylacetamide) inhibits only
the Ebola virus, while Compound 3.3 (an adamantancarboxamide),
closely related to Compound 3.0, inhibits only the related Lassa virus.
By examining the chemical properties of the two similar compounds,
this study aims to understand how these two molecules specifically
inhibit their respective viruses.
This experiment produces variations of Compound 3.0 and
Compound 3.3 through organic synthesis reactions. It then analyzes
the effect of these variations on inhibiting the Ebola and Lassa virus
infections. The study ultimately identifies some key chemical features
Illustration by Shimwoo Lee
of Compounds 3.0 and 3.3 that are important in their function as

inhibitors, which may help in the development of a new antiviral drug
to treat the deadly Ebola virus. —Jenny Lu ‘14
References:
1. “Ebola Hemorrhagic Fever”. Medline Plus Medical Encyclopedia. US National
Library of Medicine/NIH. 28 August 2009. <http://www.nlm.nih.gov/
medlineplus/ency/article/001339.htm>
2. “Known Cases and Outbreaks of Ebola Hemorrhagic Fever, in Chronological
Order.” Center for Disease Control. 25 Aug 2006. <http://www.cdc.gov/ncidod/
dvrd/spb/mnpages/dispages/ebola/ebolatable.htm>.
The Role of the Informal Sector in Equitable equitable, because there is evidence of regressive pricing. Poorer
households actually pay a higher proportion of their incomes than rich
Water Distribution: A Case Study of the Tanker households for water. Therefore, market mechanisms in Ayn al-Basha
Market in Ayn al-Basha, Jordan by Sarah Hinkfuss inequitably fulfill demand for a resource necessary for survival – one
p. 103 that many take for granted. —Jen Gong ‘12
Whether it’s smart, flavored, or vitamin-enriched, water always References:

seems to be available. In the United States, fears of water scarcity have 1. http://www.who.int/features/factfiles/water/en/
only hit the media in the last two years, and despite the more obvious
short-term consequences, the debate over water resource allocation
is nonexistent compared to the debate over global warming. In many
ways, first-world countries do not even recognize water as a commodity
– the supply is regarded as endless, the price as infinitesimally small.
However, according to the World Health Organization, in March 2009,
around 1.2 billion people (20% of the world’s population) lived in areas
of the world with a physical lack of water [1]. Though essential to life
everywhere, in many regions of the world, water is not available in
seemingly inexhaustible quantities.
One such region, discussed in this paper, is the Emir Ali neighborhood
Illustration by Shimwoo Lee
of Ayn al-Basha, Jordan. In this area, the government has a monopoly

in the water market. However, because Jordan’s supply of water per
capita is one of the lowest in the world, this market, called the formal
sector, is not able to adequately satisfy demand. Because of this, an
informal sector of the market has arisen, where tanker trucks make
profits by selling water to households. This paper seeks to examine the
impact of this new sector on the equity of water distribution. While
the formal sector is able to assure equitable distribution, the informal
sector offers a free market alternative to the government monopoly.
The study finds that while the informal sector does not discriminate
according to race, ethnicity, or religion, the market is not entirely
www.thurj.org 73
SUMMARIES Volume 3 Issue 2 | Fall 2010
Minimum Assignment Problem by Olga Zverovich (which can only take values of true or false), can we choose values for
p. 116 each of these variables such that the expression evaluates to true? In
1971, Stephen Cook determined that if this problem can be solved in
Despite the abstract sound of “complexity theory,” its actuality is polynomial time, then all problems in NP can be solved in polynomial
quite useful in mathematics and computer science. Formulated in 1971 time and are referred to as easy. The Minimum Assignment Problem
by Stephen Cook, the P versus NP question asks: if a computer can extends this question by asking if, for two classes of formulae where
determine whether a given solution is correct quickly, can it also solve the SAT is easy, it is possible to satisfy Boolean formulae by partially
the problem quickly? Not only does this question have a million dollar assigning values to the variables. The author shows that this question
prize riding on the first correct solution, it also holds the key to the is easy within a particular class of formulae in this set, called “directed”
security of our private information. A problem where a computer can 2-CNFs. The paper then generalizes both the Satisfiability Problem
determine the solution quickly is said to be of class P. If the computer and the Unsatisfiability Problem for Boolean polynomials in a similar
can verify a solution to the given problem quickly, the problem is said to manner, and shows that they are easy for linear polynomials and NP-
be of class NP. Saying that P = NP means that a problem whose solution complete for quadratic ones.
can be verified in polynomial time can also be solved in polynomial The extension of the SAT means we can push further into the P=NP
time. Polynomial time means that the time it takes for an algorithm to question and understand more about complexity theory. There are
run is determined by the size of the input to some power. In computer incredible implications to this result, particularly in Internet security
terms, that’s fast. and cryptography. These fields depend on the fact that it is incredibly
This paper addresses the Minimum Assignment Problem, an difficult and time-consuming to go through keys and passwords to
extension of the Satisfiability Problem (SAT), whose result is already hack into other people’s information. If P = NP, however, all of these
known. The SAT asks: given an expression with only Boolean variables problems can be solved in polynomial time, making it far too easy to
break into other people’s private information. —Jen Gong ‘12
Development of an automated head-fixed
Photo by Kate Xie

preparation to study the neuronal mechanisms of
motor learning in rodents by Kate Xie p. 123
The complex network of nerve cells in high-level organisms, such
as mammals, brings life to a profound range of activity. Despite their
critical role in brain function, however, researchers before have been
limited in their scope of study, largely only being able to study the
mysteries of neuronal activity in inactive and asleep subjects.
The development of a voluntary head-restrained rodent
preparation discussed in this paper, however, now provides the key
to expanding the presently limited knowledge of motor sequences
and their neuronal circuitry. Using a head-plate implantation and a
head-restraining apparatus, animals can now be more closely studied
while they are awake, and researchers are finally able to assess motor
sequences and the associated circuitry in greater depth. This technique
also opens up the horizons of understanding in other divisions of
behavior, including vision and olfaction. Due to the voluntary nature understanding of circuitry in the rodent model, this method could lead
of the head restraint, this research could also lead to the development to similar advances in even higher-level animals, including humans. This
of the automated training of animals, which holds potential for insight would be an important milestone in discovering potential treatments
into learning-related behaviors. for motor disorders and other behavioral aberrations associated with
By giving researchers the potential for a more developed incorrectly functioning neuronal circuitry. —Saima Mir ‘14

Volume 3 Issue 2 | Fall 2010 RESEARCH
Surface morphology and electrical

properties of GaN layers and AlGaN/GaN
Materials
Science
high electron mobility transistor (HEMT)
structures grown by molecular beam epitaxy
Michael Lindeborg ‘14
University of California, Santa Barbara, Materials Department
GaN and AlGaN/GaN are group-III nitride semiconductors with outstanding opto-electronic and microelectronic
application potentials. Understanding their optimal preparation techniques and final compound structures will
allow for the production of more efficient semiconductors. This study focuses on GaN epilayers and AlGaN/GaN
HEMT structures grown by molecular beam epitaxy (MBE). A series of different MBE growth conditions were
selected to map out regions with optimum structural quality and electrical performance. These epilayers were
characterized using atomic force microscopy and Hall effect measurements. Under high-temperature growth
(T>760°C), GaN exhibited superior surface structure with low RMS (root-mean-square) surface roughness when
the Ga/N flux ratio was close to stoichiometric conditions (Ga/N ~ 1). In addition, electron mobility decreased
with thermal etching of the underlying GaN substrate and Si overdoping. For both GaN and AlGaN/GaN,
decreased RMS surface roughness also improved electron mobility. Our research further defines the optimal
growth conditions and characteristics of an efficient group-III nitride semiconductor. This study can ultimately
aid in the development of more energy efficient technologies.
Introduction dislocation densities in heteroepitaxial film growth, as well as to

reduce unintentional impurity incorporation, further enhancing
This study investigated a novel class of group–III nitride semicon- the film quality. The major growth regions in the higher tempera-
ductors, which have outstanding optoelectronic and microelectronic ture range include a Ga-rich step-flow growth region, a Ga-rich
application potentials. Focus was placed on GaN epilayers and layer-by-layer growth region, and an N-rich layer-by-layer growth
AlGaN/GaN HEMT structures grown by molecular beam epitaxy region. Some additional growth modes, including Ga-droplets and
(MBE). 3D growth, are easier to obtain at temperatures lower than ~760 °C
GaN crystals provide a promising material with which to employ [4]. Further study is required to fully characterize the newer growth
their high-quality electrical properties for a number of applications. regions and to optimize the material properties of the GaN films
They have shown success in their use in electronic devices, such created within them. In this study, PAMBE GaN films were grown
as RF power devices and amplifiers, demonstrating an ability to in the temperature range of 780-795 °C, providing insight into the
withstand high power loads and frequencies, breakdown voltages characterization of the upper end of studied growth regions.
of 3 MV/cm and thermal conductivities of 130 W/mK [1,2]. Electron With respect to the second part of this study, high electron
mobilities as high as 1150~1190 cm2/V·s have been achieved with mobility transistors (HEMTs) have a vast potential in applications
films grown in plasma-assisted molecular beam epitaxy (PAMBE) including cell-phones, direct broadcast satellites, and radar because
systems [3], creating further advantages to their use in semiconduc- of their direct band gaps, high voltage, and high power [4]. HEMTs
tor high-speed electronics. are based on various semiconductor combinations with two different
In this study, two separate types of investigations were per- band gaps, which are regions of energy between the valence band
formed: on bulk GaN epilayers and AlGaN/GaN HEMTs. In the (VB) and the conduction band (CB) where electrons cannot propa-
first type of study, various MBE growth conditions were analyzed gate. HEMTs are made of a variety of compounds such as GaAs,
and several types of film growth modes were characterized, primar- InP, or SiC. However, nitrides, such as the AlGaN/GaN structures
ily dependent on the Ga/N flux ratios and growth temperature [3]. (Figure 1), make the AlGaN/GaN HEMT more effective than other
Much of the previous work done on the study of GaN has focused kinds of HEMTs. Nitrides’ advantageous properties include a stable
on growth regions with relatively lower temperatures. Only recently wurtzite crystal structure. This structure creates covalent bonds
have the growth modes for GaN in higher temperature regions with and a high thermal conductivity, both of which are necessary for
PAMBE begun to be characterized [3,4]. The growth regions in these heat dissipation out of a HEMT [5]. The high thermal conductivity
temperature ranges have provided films with properties comparable of the nitrides therefore allows the HEMTs to be useful in a wider
to the best of those grown in lower temperature regions [5]. Higher range of applications [4]. Another important property of nitrides is
growth temperatures were used to further reduce the threading the high velocity of the electron-carriers, which allows for greater
www.thurj.org 75
RESEARCH Volume 3 Issue 2 | Fall 2010
Figure 1. (left) Structure of AlGaN/GaN showing

polarization
Materials
Science
Figure 2. (right) GaN growth diagram: blue

points represent the growth conditions studied.
They dominate the N-rich lb-l region; conditions ex-
ist in the Ga-rich step-flow and Ga-rich l-b-l layers.
electron-carrier mobilities and higher voltages and further enhances (manufacturer: Lumilog), with dislocation densities of 5x108/cm2,
the HEMTs [4]. Nitrides also carry a larger internal electric field served as the substrate material. The beam flow rates and substrate
up to one order of magnitude greater than that of GaAs. These all temperature were varied widely to produce a wide range of growth
contribute to making an effective HEMT. Analysis of AlGaN/GaN conditions. In addition, thermal etching, by which GaN-template
samples will determine specific trends in electronic properties that substrates were heated to remove varying amounts of impure surface
create a more proficient HEMT. material, and silicon doping were also applied to some samples. Ga-
An electric field existing between a heterojunction of two dif- flux ranged from 2-14 nm/min, and the N-flux was held constant at 5
ferent materials with a high and low band gap creates an effective nm/min for all samples. Growth temperatures ranged from 780-795
HEMT. In this case, the two materials are AlGaN and GaN. As °C, and thermal etching thickness ranged from 0-50 nm. Silicon
a result of the heterojunction, internal strain is created at the doping on samples, when applied, ranged from cell temperatures
AlGaN/GaN crystal interface (the active region), which results in of 1140-1300 °C, corresponding to concentrations of ~1016-1018 cm-2.
a larger piezoelectric polarization. In addition to the piezoelectric Such variations resulted in significant changes of film properties
component, the nitrides also contain a large internal spontaneous and surface morphology, which were categorized in one of several
polarization due to the polar direction of the crystals. The polar- growth regions based on these conditions [3,10]. The relatively slow
ization-induced electric field affects the two different materials, growth rates when using MBE allowed for precise control of the
causing the conduction and valence bands to bend. At the hetero- film thickness. Real-time, in situ, monitoring of crystal growth was
junction, the different band gaps of the materials create a quantum accomplished through the use of Reflection High Energy Electron
well where the 2-dimensional electron gas (2DEG) resides (Figure Diffraction (RHEED) [8,9]. The diffraction pattern was indicative of
1) [6]. Without bending bands, the electrons would normally be the current surface condition of the sample. Combined, slow growth
equally distributed along the conduction band on GaN; however, rates and RHEED monitoring allowed for very precise control of
the quantum well creates a “sea of electrons” restricted to flowing crystal growth. Once wafers of the crystal film were grown, they
along the heterojunction. HEMTs can be enhanced by improving were cut with diamond scribes into approximately 1 cm2 square
the 2-DEG mobility and density, making a high-speed channel for samples to be further analyzed.
electrons (Figure 1) [7]. By analyzing specific properties of AlGaN/
GaN, such as its surface morphology and the electronic properties, Electrical properties analysis
the effectiveness of a HEMT can be determined. The carrier density and carrier mobility of the GaN and AlGaN/
GaN films were determined by the use of a Hall effect measurement
set-up and the Van der Pauw method. The four ohmic contacts
Materials and methods required by the Van der Pauw method were made of indium metal
soldered onto the corners of the sample. Placement of the indium
contacts as close to the edge as possible, as well as a regular square
Crystal growth geometry, were required for ideal measurements [11]. The sample
Gallium nitride thin-film crystals and AlGaN/GaN HEMT’s was then placed onto a contact card, which was inserted into the
were grown in a Veeco Gen II plasma-assisted molecular beam Hall set-up. In the apparatus, the sample card was placed between
epitaxy (PAMBE) system. Growth took place in a highly-controlled two strong electromagnets that provided the magnetic field in which
ultra-high vacuum (UHV) environment, where the background the Hall effect could be observed. Computer software measured and
pressure of the chamber was on the scale of 10-9 torr [8]. The react- recorded all data. Current and voltage measurements were taken
ing gallium and aluminum were held in quasi-Knudsen cells, where along each side of the sample. From Ohm’s Law, the resistivity
they were sublimated into a vapor phase by the maintenance of a values were calculated. The Hall setup then applied the magnetic
sufficiently high melting temperature [9]. The gallium and alumi- field, and the computer software calculated the carrier density and
num beams were directed from the cell to a substrate material in carrier mobility of the sample as determined by standard Hall effect
the growth chamber, where film growth occurred as the gallium theory [12].
reacted with nitrogen that was generated by an rf-plasma from an
external source [9]. Iron-doped, semi-insulating GaN templates
Materials
Science
Figure 3a. Surface morphologies of GaN grown at 780 °C with varying Ga- Figure 4a. Surface morphologies of GaN films at 770 °C with varying Ga-flux
flux.
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Surface morphology analysis Results

The surfaces of the GaN and AlGaN/GaN samples were imaged
using atomic force microscopy (AFM). Veeco models D3100 and After all GaN and AlGaN/GaN samples were grown via PAMBE,
D3000 were used to conduct the AFM scans. AFM creates images of they were characterized with AFM imaging and Hall effect measure-
the surface of the sample by measuring the deflection of a microm- ments. The sixteen different sets of growth conditions of GaN films
eter-long silicon cantilever and tip mechanism [13]. Tip deflections covered much of the N-rich layer-by-layer (l-b-l) growth region,
are a result of Van der Waals forces, electrostatic forces, and other though there were samples from the Ga-intermediate region, with
intermolecular forces between the tip and sample surface. Our both l-b-l growth and step-flow growth (Figure 2). There were fif-
scans were completed in AFM tapping mode, in which a piezoelec- teen samples of aluminum gallium nitride (AlGaN/GaN) that were
tric actuator vibrates the tip at its resonant frequency, which was tested. By characterizing certain sets of samples, trends in electrical
approximately 300-350 kHz. Tip-surface interactions affect the tip’s properties and surface morphologies were deduced from growth
oscillation amplitude, from which the surface contour maps can be conditions.
made. The actual deflection of the tip is measured by a laser aimed
at the cantilever. Tip deflections move the reflected image of the GaN epilayers:
laser, which is measured by a photo-detector [13].
Real-time modifications of tip parameters were used to opti- Ga-flux variations and RMS roughness
mize measurement noise. Image scan sizes ranged from 1-100 μm2. Samples grown at 780 °C with varying Ga-fluxes showed a dis-
After raw images were taken, they were processed with Nanoscope tinct trend in surface morphology. Ga-fluxes of 14, 7.5 and 4 nm/
image software to acquire image height ranges (Z-range), roughness min resulted in root-mean-square (RMS) roughness of 1.8, 1.0, and
(RMS-roughness), feature dimensions, and three-dimensional maps 0.5 nm respectively (Figure 3a). Image a demonstrates a stepped
surface with clear ridges as well as pits. The surface in image b has
a flatter and smoother overall morphology; however, it still exhibits
pits, which is indicative of the termination of lattice dislocations
www.thurj.org 77
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Materials
Science
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Figure 5 (top), Figure 6 (bottom) Figure 7 (top), Figure 8 (bottom)
within the crystal. Image c lacks any clearly defined pits and has RMS roughness is lowered (Figure 4b).
much more homogenous surface features.
The RMS roughness values sharply decreased as the Ga-flux was Variations in growth temperature in the N-rich growth regime
lowered, transitioning through the growth regions from Ga-rich Samples grown at the same Ga-fluxes as above, but with vary-
step-flow, to Ga-rich l-b-l, to N-rich l-b-l. Moving from high to more ing growth temperatures, exhibit a similar RMS roughness trend.
equal Ga/N ratios resulted in empirically smoother samples. The Morphologies of GaN films were grown with Ga-fluxes of 2, 3, and
growth mode diagram shows that the high Ga/N ratios result in 4 nm/min, and at temperatures of 785, 788, and 795 °C, respectively.
step-flow, where more equal ratios result in l-b-l growth. Therefore, Images at 2 nm/min showed a very rough surface, with hexago-
there is a correlation between l-b-l and smoother surfaces. This nally shaped, tower-like 3D structures. These towers had a height
trend appears closely linear at constant temperature (Figure 3b). of at least 38.0 nm. Consistent with the GaN films grown at 770
Samples grown at 770 °C also showed a clear trend in RMS rough- °C, the RMS roughness decreased as the Ga-flux approached the
ness with variation in Ga-flux. Films grown with 4, 3, and 2 nm/min fixed N-flux of 5 nm/min: films grown with Ga-fluxes of 2, 3, and
Ga-fluxes showed RMS roughness values of 3.9, 7.1, and 19.4 nm, 4 nm/min had RMS roughness values of 10.4, 9.2, and 1.4 nm,
respectively on 10 µm × 10 µm images (Figure 4a). These samples respectively on 10 µm × 10 µm images (Figure 5). Other scan sizes
were all in the N-rich region and showed a RMS roughness trend showed the same general trend; however, only the 1 µm × 1 µm
opposite to the previous set of films. Image a is mildly smooth, but scan demonstrated a clear linearity. As shown in Figure 4a and
clearly shows surface features that indicate suppressed gallium and b, surface roughness increased due to the very low Ga/N ratios.
nitrogen diffusion along the surface. Image b shows a similar case, Without enough gallium, surface diffusion could not occur and
but to a rougher extent. Image c contains scale-like, jagged features rough features, such as towers, accumulated.
which make it the roughest of all images in this series. In this set
of conditions, RMS roughness varied inversely with Ga-flux. This GaN sub-layer and surface morphology
demonstrates that when Ga/N flux ratios are too low, as in sample c, Surface morphology was also affected by the addition of a
there is not enough gallium to facilitate surface diffusion, resulting 100-nm-thick, Ga-rich, GaN sub-layer below the N-rich GaN epi-
in rougher films. Thus, as the Ga-flux approaches the fixed N-flux, layer. The buffer layer was grown at 700 °C with a Ga-flux of 8 nm/
Materials
Science
Figure 9 Figure 10
min and N-flux of 3.5 nm/min. Two samples with and without this other growth parameters, including thermal etching and Si-doping.
GaN buffer layer were grown at 785 °C with a Ga-flux of 4 nm/min
and an N-flux of 5 nm/min. Each was approximately 0.4 µm thick. Silicon doping and electron mobility
The film with the GaN buffer layer showed a RMS roughness of The concentration of the silicon dopant added to GaN films
2.3 nm for the 10 µm × 10 µm scan and 0.9 nm for the 1 µm × 1 affected electron mobility as well. The addition of charge carriers
µm scan. The largest single peak/valley was 29.8 nm in the sample increased carrier density, although the dopant atoms generally
without the buffer layer, but only 7.5 nm in the buffer layer sample. did not fit into the existing crystal lattice, causing crystal defects
This value was significantly lower in the sample with the buffer layer, which reduce mobility. Therefore, increased doping increased carrier
which had a RMS of 6.2 nm for the 10 µm × 10 µm scan and 3.4 density but also decreased mobility. Figure 7 shows the relationship
nm for the 1 µm × 1 µm scan. Clearly, the GaN sub-layer positively between the concentration of silicon dopant and electron mobility
affected the surface smoothness of the film. in the GaN films. The graph plots Si-doping in terms of the cell tem-
perature at which it was deposited into the film. Cell temperature
Thermal etching thickness and electron mobility is directly related to the concentration of the Si-dopant, which can
Etching of GaN templates was performed in situ within a vacuum be used as a means of comparison. The graph demonstrates that a
in the MBE chamber at elevated temperatures (780°C) in order to maximum electron mobility of 718.0 cm2/V·s was achieved at a Si-
remove any potential surface impurities (typically Si, O, H and cell temperature of 1140 °C. As silicon concentration was increased
C). The heat caused the surface of the film to effectively bake off, with cell temperatures of 1200, 1260, and 1300 °C, electron mobility
therefore reducing the thickness of the film. The purpose was to diminished to 147.4, 179.0, and 66.9 cm2/V·s. Thus, over-doping the
try and remove impurities on the surface, but at the same time, the GaN film causes excessively high levels of silicon impurities, which
heating could introduce structural imperfections into the crystal. trap electrons and significantly reduces mobility.
This could lead to electron traps and scattering centers, which reduce In silicon-doped samples, a distinct relationship between elec-
mobility. Similar to RMS roughness, determination of the electron tron concentration and electron mobility was apparent, as shown in
mobility of the GaN films prepared with this etching step was criti- Figure 8. As electron concentration was increased, electron mobility
cal to proper understanding of the overall material quality. As with was significantly affected. Concentration values of 6.8 1016 cm-3, 1.0
surface morphology, several trends in electron mobility exist. Figure × 1017 cm-3, 1.3 × 1018 cm-3, 1.5 × 1018 cm-3, and 8.9 × 1018 cm-3 had
6 shows the effect of thermally etched GaN-template substrates decreasing electron mobilities of 718.0, 453.2, 179.0, 147.4, and 66.9
before growth on electron mobility. As etching was increased at 10, cm2/V·s. This relationship is nearly inverse proportional where nµ =
25, and 50 nm, the mean electron mobility decreased to 310.7, 285.1, k, n is electron concentration, and µ is electron mobility. The actual
156.1 cm2/V·s, respectively. This suggests that larger etching thick- curve yields n0.46 as opposed to n1; k was approximately 10 V-1s-1.
nesses most likely promoted the development of defects, yielding
electron traps within the film, and thus restricting the free move- AlGaN/GaN HEMTs:
ment of carriers. Typically, thermal etching reduces impurities at
the GaN/GaN-template interface. Unlike etching, RMS roughness AlGaN thickness in AlGaN/GaN structures and 2DEG Hall Mobility
appeared to have no direct effect on electron mobility; however, The samples measured were grown at similar conditions (same
such an expected trend could be obscured by the interference of Ga/N and (Al+Ga)/N ratio) with varying temperature between
www.thurj.org 79
be seen in Figure 10, which is similar to the trend for the AlGaN
thickness study. Aluminum composition and aluminum thick-
ness are closely related. Parabolic shaped Hall mobility curves
were present for both experiments. As a result, an optimum Al
Materials
Science
composition and AlGaN thickness was found at which Hall mobil-

ity was at a maximum. In this set of data, the Al composition at
which Hall mobility was highest occurred at 25%. This result may
be explained by postulating that too much Al composition creates
an overabundance of electron scattering centers in the layer, which
has adverse effects on the mobility. Also, the data indicated that
the Hall mobility was affected by the surface RMS roughness. As
shown in the AFM images in Figure 10, higher RMS roughness
yielded a lower Hall mobility.
Sheet Carrier Density and Hall Mobility

A relationship was identified between the 2DEG Hall density and
the Hall mobility for the same samples of AlGaN/GaN prepared
with a buffer doped with carbon. In Figure 11, 2DEG Hall density
ranges between the values of -1.06 × 1013 to -2.94 × 1013 cm-2, which
is relatively higher than the typical values obtained from samples
with merely the gallium-rich buffer samples. The graph shows that
with increasing 2DEG Hall density causes a decrease in the Hall
mobility. As shown by the samples 052008A-051508A, the 2DEG
density increased from -1.06 × 1013 to -1.82 × 1013 cm-2, and the
Figure 11 Hall mobility decreased dramatically. However, from 051508A to
060208A, the curve became more constant and tapered off between
densities of -1.82 × 1013 and -2.94 × 1013 cm-2. Thus, an inverse rela-
770-790°C and all contained a gallium-rich buffer. Thermal etch- tionship exists between Hall density and Hall mobility—as Hall
ing of the underlying GaN substrates was also performed among density increases, Hall mobility decreases. As observed previously,
some samples, with etching thicknesses ranging between 0-200 nm. an increase in RMS roughness leads to a decrease in Hall mobility.
When comparing the Hall mobility to aluminum thickness of the This observation holds true for all samples grown under similar
AlGaN/GaN layer in Figure 9, a distinct parabolic trend could be growth conditions.
identified. Hall mobility increased as AlGaN thickness increased,
and a maximum Hall mobility was achieved at an AlGaN thickness 2DEG characteristics between carbon-doped and Ga–rich buffers
of 33 nanometers, after which larger thicknesses negatively affected Another analysis investigated the effects of the gallium-rich
mobility. When analyzing the surface morphology of the various buffer, the carbon-doped buffer, or no buffer on the 2DEG charac-
AlGaN layers, a distinct trend was also observed with AlGaN thick- teristics, which function to bury the impurities caused by crystal
ness. According to the AFM images shown in Figure 9, larger AlGaN mismatch with the substrate during wafer growth. In this com-
thicknesses created higher root mean squared (RMS) roughness parison, the purpose was to determine which buffers allow for
values as compared to lower thicknesses. This discrepancy was a greater mobility among these samples prepared under similar
most likely due to the typical statistical roughening, which occurs growth conditions. These conditions were growth temperatures in
at increased layer thicknesses. The increased RMS roughness is the range between 770-795°C and an even distribution of aluminum
correlated with decreased Hall mobility and, hence, a less effective composition between the types of samples. A significant trend
AlGaN/GaN HEMT could be expected. For AlGaN thicknesses appeared between the gallium-rich buffer and the carbon-doped
greater or smaller than 33 nm, RMS roughness is higher and Hall buffer samples. They both had parabolic curves which followed the
mobility is lower. same paths. However, the carbon-doped buffer samples had higher
Hall mobility. Higher Hall mobility was also positively affected by
Al composition in AlGaN/GaN structures and 2DEG Hall mobility the RMS roughness of the samples. Two different samples (031708A
The samples measured were grown at similar conditions with and 032608A) with similar aluminum composition (27%, 28%)
temperatures varying between 770-790 °C. However, these samples but different buffers were analyzed. Sample 031708A contained a
were prepared utilizing a carbon-doped buffer. The carbon-doped gallium-rich buffer and sample 032608A had a carbon-doped buffer.
buffer was used to generate a semi-insulating GaN buffer, isolating Measured at a 10 µm × 10 µm window, the sample with the buffer
the 2DEG active region from the regrowth interface, where a para- doped with carbon had a RMS roughness of 8.0 nm while the gal-
sitic conductive channel might preside due to residual impurities lium-rich buffer had a RMS roughness of 10.3 nm. Therefore, RMS
not sufficiently etched. Most of the underlying GaN substrates were roughness decreases as the Hall mobility increases. These factors
thermally etched by 25 nm except for sample 021208A, which was indicate the ideal conditions sought after when creating a HEMT.
significantly smaller when etched at 25 nm than at 200 nm. The
relationship between aluminum composition and Hall mobility can

Discussion ratios. This was reflected by differences in electron mobility within

GaN layers, with adverse effects also found by thermal etching of
GaN film RMS roughness values show a clear relation to Ga-flux the underlying GaN substrate and Si-overdoping. For AlGaN/GaN
(Ga/N ratio) for GaN films grown at high temperatures. In Ga- HEMTs, similar trends were observed, i.e. an increase in electron
Materials
Science
rich conditions, decreasing the Ga/N results in smoother surfaces, mobility of the two–dimensional electron gas with decreasing RMS
whereas in N-rich conditions, increasing Ga/N results in smoother roughness. Carbon-doped GaN buffers in AlGaN/GaN samples
surfaces. Both of these trends have linear properties and show the showed higher electron mobilities than samples grown without buf-
smoothest surfaces close to flux stoichiometry when Ga/N~1. The fers. Finally, a parabolic relationship between electron mobility and
reason for the increase in RMS roughness when deviating from the aluminum concentration and AlGaN thickness was determined for
Ga/N ratio of 1 lies in the enhanced thermal decomposition under layers grown at constant Ga/N flux ratio. Future research in this area
Ga-rich conditions (Ga/N >> 1) and the lack of sufficient surface can better define the optimal growth conditions, which may result
diffusion under N-rich conditions (Ga/N << 1). Ga-rich buffer lay- in the most efficient nitride-based semiconductors and HEMTs.
ers appear to improve surface morphology of the top N-rich grown
GaN films. Increased thermal etching thickness, as well as silicon
over-doping, negatively affects electron mobility. Silicon-doping References
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ables, which can be modified to affect the electronic properties of Semiconductor Materials GaN, AlN, InN, SiC, SiGe. Wiley, New York, 2001.
the structure. All of the trends identified in the study included a 3. Heying, B., I. Smorchkova, C. Poblenz, C. Elsass, P. Fini, and S. Den Baars.
relation to Hall mobility through aluminum composition, thick- “Optimization of the Surface Morphologies and Electron Mobilities in
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sample. The most effective HEMTs are created when the aluminum 4. Shur, Michael. “Heterostructure Field Effect Transistors.” 2007. 23 July
composition is at 25% or the thickness of the aluminum in the 2008 <http://nina.ecse.rpi.edu/shur/sdm2/Notes/Notespdf/18HFET.pdf>.
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tion was determined concerning carbon-doped samples in which John Wiley and Sons Ltd., 1980.
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9. Feick, Henning. “MBE Growth of GaN.” 18 Dec. 2001. Berkeley U. 17 July
2008 <http://www.mse.berkeley.edu/groups/weber/research/ganmbe.html>.
Conclusion 10. Koblmüller, G., S. Fernández-Garrido, E. Calleja, and J. S. Speck. “In Situ
Investigation of Growth Modes During Plasma-Assisted Molecular Beam
Group-III nitride semiconductors have been shown to have out- Epitaxy of (0001) GaN.” Applied Physics Letters 91 (2007). 21 July 2008.
standing optoelectronic and microelectronic application potentials. 11. Van Der Pauw, L. J. “A Method of Measuring Specific Resistivity and Hall
These investigations identified various growth conditions that posi- effect of Discs of Arbitrary Shape.” Philips Research Reports 13 (1958). 23
tively and negatively affect the performance of both GaN epilayers July 2008.
and AlGaN/GaN HEMTs. It was found that under high–tempera- 12. Serway, Raymond A. Physics for Scientists and Engineers. 4th ed. Philadel-
ture growth (T > 760°C), superior surface structure with low RMS phia: Saunders College, 1996.
(root-mean-square) surface roughness was achieved when the Ga/N 13. Carpick, Robert W. “Scratching the Surface: Fundamental Investigations
flux ratio was close to stoichiometric conditions (Ga/N ~ 1). Higher of Tribology with Atomic Force Microscopy.” Chemical Reviews 97 (1997):
roughness resulted from higher (Ga/N > 1) and lower (Ga/N < 1) flux 1163-1194.
www.thurj.org 81
Who has the right to define place:

Authenticity in Boston’s Latin Quarter from
the perspective of white gentrifiers and old
timers
Melissa Deas ‘10
Harvard University, Department of Sociology

Sociology
Who has the “legitimate” right to define a place’s identity? In this ethnographic study I use the frame of a plan
to rebrand a gentrifying Boston commercial district as Boston’s Latin Quarter to examine this question. Look-
ing at the perspective of white gentrifiers and Latinos I analyze how these groups understand this question. I
will argue that white gentrifiers’ support of or opposition to the name change reflects their own internal inse-
curities about their role as gentrifiers and members of the community. Even more, both white gentrifiers who
support and who oppose the name Boston’s Latin Quarter use authenticity to defend their own right, or the
right of Latinos, to define place. Interestingly, those who support the name change define authenticity in terms
of people, whereas those who oppose the name change define authenticity in terms of place. While newer Latino
residents also express concern about the name change and maintaining authenticity in the community, older
Latinos appear less concerned about authenticity and even gentrification than many of the white people in the
neighborhood. Instead, these Latinos seem to care more about gaining recognition and maintaining a sense of
cultural pride in the next generation.
Introduction the district’s identity. Overall, I show that the ways in which the
actors in this community define authenticity mirror their personal
This paper examines how white gentrifiers and Latino commu- and cultural perceptions of their own role in the community.
nity members understand authenticity within their community
and how this affects their support of a recent plan to change the
name of a Boston commercial district from “Hyde Jackson Square” Background
(HJS) to “Boston’s Latin Quarter.” While the board members of a
local non-profit—Hyde Jackson Square Main Street—are united in This paper analyzes a small urban community struggling to
their decision to rename this commercial district “Boston’s Latin define its place-based identity. To be a “place,” rather than simply
Quarter” and in their desire to define this commercial district of some abstract geographic space, a location must have an identity,
their neighborhood as a Latino place, the community’s perspec- a sense of significance attached to it that makes it meaningful
tives on this plan are complex. Through in-depth interviews with and recognizable (Gieryn 2000). The place in this study is a small
white and Latino residents and business owners, I discovered that multicultural Boston neighborhood called Hyde Jackson Square
those who live and work in the neighborhood hold a variety of (HJS), which is currently renegotiating the meaning of place as it
ideas about who has the right to define and call this neighborhood confronts gentrification. The frame of my study is a marketing plan
their home. Using Brown-Saracino’s (2004, 2007, 2009) typology implemented by a local non-profit organization (called Hyde Jack-
of gentrifiers and old-timers, this paper explores some of the issues son Square Main Street or HJSMS), which recently rebranded the
surrounding this debate: the different ideologies among white gen- commercial district of this diverse neighborhood as “Boston’s Latin
trifiers within this diverse community, the concept of Latino and Quarter.” During interviews, board members of HJSMS explained
“authentic” old-timers within the community, and the notion of that this particular re-branding decision is based on the desire to
preserving an authentic Latin Quarter. I compare the white gentri- attract people to the commercial district and celebrate the preva-
fiers’ perspectives on the neighborhood and rebranding to those of lence of Latino businesses and people in the neighborhood.
Latino old-timers, showing that the older Latino residents see the In the confines of this paper I cannot delve deeply into the com-
purpose of Boston’s Latin Quarter differently. They stress cultural plex history and demographics of this neighborhood. However, it
remembrance rather than authenticity. Also, I compare gentrifiers is important to note that the neighborhood is not entirely Latino.
who support the rebranding plan to those who do not, finding that Based on 2007 Census estimates, 43% of the population of HJS
Brown-Saracino’s typology of gentrifiers is reflected in these two identified as Hispanic, 35% as Non-Hispanic white, 16% as Non-
groups’ agendas. Additionally, I extend Brown-Saracino’s work Hispanic black, and about 4% as Asian or other (Figure 1). These
as I explore how both groups of gentrifiers use authenticity to demographics highlight how the rebranding of the commercial
frame their arguments over who has a legitimate right to define strip of the neighborhood as Boston’s Latin Quarter is a choice to
1989 1999
(1990 (2000 2007 Difference
census) census)
Tract 1205 31,490 40,968 41,737 10,247
Tract 1206 48,143 55,194 53,419 5,276
Tract 1207 36,182 45,355 42,239 6,057
Tract 812 31,990 18,967 14,816 -17,174
Averages 36,951 40,121 38,052 1,101
Table 1. Median Household Income ($) by Census Tract in HJS adjusted

for inflation in 1999
Sociology
Source: Social Explorer 2007 estimates; Social Explorer 2000 census data; So-
cial Explorer 1990 census data; U.S. Bureau of Census 1990; U.S. Bureau of
Census 2000
the inhabitants of a place change from a group that has less social
Figure 1. Racial and ethnic percentages in Hyde Jackson Square status to one with more social status. This definition is based on
Source: U.S. Census Bureau and Social Explorer Ruth Glass’s original 1964 study on a London community in which
Notes: working-class families were pushed out of their homes by more
*In 1970 all people who identified their race as “other” were included in the affluent ones. She coined the term gentrification. In her study she
white category, making it somewhat inflated.
**The “other” category is consistently about half-Asian
notes how the “working-class quarter of London” was “invaded
***2007 numbers are based on estimates created by Social Explorer by the middle classes,” transforming the “shabby, modest mews
and cottages” into “elegant expensive residences” (p. xviii). Glass
focus on just one aspect of this diverse community. continues, “Once this process of ‘gentrification’ starts in a district
It is also important to understand that this is, arguably, a neigh- it goes on rapidly until all or most of the original working-class
borhood in the beginning stages of gentrification. All of the census occupiers are displaced and the whole social character of the district
tracts in HJS, except for the one that contains a large public housing is changed” (p. xviii). The term gentrification is literal in that the
development, have seen substantial increases in median household wealthier, often white residents, the “gentry,” push out the lower
income since the 1970s (Table 1). Despite this, the neighborhood is class. As Glass highlights, gentrification not only results in physical
still racially/ethnically diverse (Figure 1), and still has many of the displacement, but a new “social character” for the neighborhood.
common signs of a working class neighborhood that Zukin (2010)
identifies: dollar stores, small bodegas, and cash advance agencies. Who are the gentrifiers?
This feeling of impending gentrification is also apparent in the When studying gentrification, it is important to identify who
words and memories of long-term community members. They the gentrifiers are within the community. Traditionally, gentri-
explained to me that in the 1970s HJS experienced dramatic white fiers are understood to be middle-class residents attracted to the
flight (Figure 1). During my in-depth interviews, long-term residents affordability of a neighborhood (Glass 1964). However, more recent
explain that with this white flight came a dramatic economic decline studies emphasize that they may be attracted to a particular place
and HJS became a hotbed of violent and often drug-related crime. for cultural, rather than economic, reasons (Zukin 2010; Brown-
While older white residents fled HJS, the neighborhood became Saracino 2009).
an affordable place for immigrants—mostly from Cuba, Puerto Scholars, such as Rose (1984), caution against treating gentrifiers
Rico, and the Dominican Republic—to open businesses and build as a single group. Rose asks an important question: “What concep-
a community. Today, many residents feel like the neighborhood is tual grounds exist for assuming that the ‘first stage’ and the ‘end
moving in the “right direction.” While there is still crime, its repu- stage’ affluent residents have anything in common other than the
tation is improving. José, who grew up in HJS, recalls that when he fact that their household incomes are higher than the original resi-
was a child the only white people he saw there were the ones who dents?” (p. 58). She asserts that gentrification is a “chaotic” process
came to buy drugs. This is no longer the case. The vast majority with a great deal of variability. She notes that the initial gentrifiers
of the people I interviewed reported that more affluent and often may be motivated by the belief that the neighborhood will be more
white residents are moving back to HJS, shopping and spending tolerant to a particular group of people (such as lesbian and gay
much more time there. While residents generally appreciate the populations) than other neighborhoods, while later gentrifiers may
fact that the neighborhood is becoming safer, many worry about be more economically motivated.
the increased cost of living. While these issues of diversity are important, Brown-Saracino
(2009, 2007, 2004) suggests a different approach to defining the dif-
ferences between gentrifiers. She argues that gentrifiers fit into three
Theoretical understandings of gentrification categories based on their ideologies surrounding gentrification and
how they define themselves as gentrifiers: 1) pioneers who ruthlessly
Gentrification is a concept that is constantly being redefined, retake space from the others; 2) social homesteaders “who engage in
negotiated, narrowed, and expanded within the literature. However, transformation of poor and working-class neighborhoods to serve
gentrification traditionally is understood as a process in which middle-class purposes,” (2009:10) but do so cautiously because
www.thurj.org 83
they are also attracted to the idea of living in a neighborhood that temporal moment in the process of gentrification, during which
is diverse and affordable; 3) social preservationists who “engage neighborhoods are multicultural and socioeconomically diverse.
in a set of political, symbolic, and private practices to maintain Zukin (2010), on the other hand, frames gentrifiers’ desire for
the authenticity of their place of residence, primarily by working authenticity in terms of place rather than people. She argues that
to prevent old-timers’ displacement” (2009:9). Interestingly in her the search for authenticity is motivated by people searching for a
discussion regarding this last point she notes that in three out of sense of real connection to a place: “Though we think authenticity
her four studies these “old timers” belong to a racial or ethnic refers to a neighborhood’s innate qualities, it really expresses our
group different from the gentrifiers—they are Portuguese fisherman, own anxieties about how places change” (p. 220). Authenticity is
Swedish immigrants, or Asian merchants while the gentrifiers are about a need to feel that those places and neighbors that are here
white. When I apply Brown-Saracino’s typology of gentrifiers to today will be here tomorrow. It is about the search for a place that
HJS, I contend that the old-timers are arguably the Latino popula- will be invested with the same sets of meaning over time. This is
tion and that gentrification is, at least in part, reflective of a social impossible, since each social actor in the neighborhood has his or
preservationist model. her own image of when and how the neighborhood was authentic.
Sociology
Moreover, in Zukin’s opinion, the presence of gentrifiers in these

Who or what is worth preserving? neighborhoods will, by their own consumptive practices, set into
Through my research it became obvious that authenticity is a motion homogenizing forces that recreate these places into white
primary concern within the neighborhood, particularly in the face urban neighborhoods.
of changes brought on by gentrification. Residents and business This paper does not focus on whether or not authenticity is pos-
owners worry that this new place-identity, Boston’s Latin Quarter, sible, nor does it attempt to answer the question of why people are
will create something artificial. Others worry that if Latinos are attracted to authenticity. Instead it uses Brown-Saracino’s typology
entirely displaced, this authentic Latino enclave will be destroyed. of gentrifiers to investigate the white gentrifiers’ and Latino old-
Zukin (2010) observes that the term authenticity “has crept into timers’ perspectives on Boston’s Latin Quarter and their use of
popular language in the past few years” (p. xi). Increasingly, it is authenticity to defend these opinions. It extends previous research
seen as beneficial to claim authenticity in both the sense that a by showing that each category—social preservationist, social home-
place is historical and traditional, as well as the sense that it is steader, and old-timer—uses a different definition of authenticity
“unique, historically new, innovative and creative” (p. xi). Cities to justify its beliefs.
market themselves as “authentic” because people increasingly travel
searching for authentic tastes, experiences, and smells (also Judd
2003). Gentrifiers also move to places they identify as authentic Methods
(Brown-Saracino 2009, 2007, 2004; Zukin 2010). Clearly there is a
strong drive for authenticity, but why? In addition to my experiences living and working in the com-
Brown-Saracino (2009, 2007, 2004) points out that there are munity over the span of two summers, the primary data used in
certain “authentic” groups that become the focus of social pres- this paper comes from 49 in-depth interviews collected over the last
ervationist movements. These gentrifiers identify “old-timers” in two years11. The majority of the respondents live in the HJS area.
a neighborhood as valuable because they see these people as more Nineteen owned or worked in businesses within HJS. Eighteen
“authentic” than themselves. In her description of old timers she worked at and/or had served on the board of a local non-profit
notes some specific characteristics: “social preservationists appreci- agency. Eight were on the current board of directors for HJSMS.
ate those who appear autonomous: who seem to live a ‘simple’ life Others lived, but did not work in the neighborhood. There was a
and depend on their own labor, land, bodies, families, and local great range in the number of years participants lived or worked
networks” (2007:446). They are the farmers or the merchants. She in HJS, with the average being 17. My interviewees also ranged in
observes that social preservationists define old-timers as possess- age from 19 to 76 years. About half of my sample was white, and
ing “qualities they associate with real community and that they half were Latino. Additionally there was one African American
believe they do not personally possess: independence, tradition, participant and two Asian participants.
and a place-based way of life” (2009:153). These people are not only In this paper I attempt to apply Brown-Saracino’s typology
seen as having long-lasting ties to the community, but also as living of social preservationist, social homesteaders and pioneers. It
in more traditional and arguably anti-modern ways. The fact that is important to note that this typology is an oversimplification.
white respondents in HJS often described Latinos as hard-workers While gentrifiers are generally framed as a more affluent class of
and independent small business owners with strong family tradi- people, there is also an assumption that gentrifiers tend to be white
tions validate Brown-Saracino’s observation. (Brown-Saracino 2009). However, there is evidence that an influx
Brown-Saracino’s (2009) description of social preservationists of middle-class people of color would have similar impacts on
also suggests that the desire for authenticity is rooted in both nos- neighborhoods because change due to gentrification may be more
talgia and the desire for stability over time. She finds that social a result of consumption practices based on class position rather
preservationists “express nostalgia for ‘traditional’ community
rooted in fear of the constant evolution of space” (p. 152), that is, 1. As I begin to present data from my interviews I ask my reader to remember
that my respondents cannot possibly be representative of all people within HJS.
they worry further gentrification will destroy authenticity. However As Small (2009) argues, each represents one case-study that provides a window
at the same time “social preservation is not an effort to return to into this particular community. While each interviewee’s words and perspectives
an earlier era. Rather, it is an effort to prevent change, to freeze a on their community are valid, they do not necessarily represent the views of oth-
ers in the community. While the opinions in this paper are not representative,
place before gentrification alters it” (Brown-Saracino 2004:152-53). they are congruent with my own experiences living, working, and interacting
In this sense, authenticity represents a desire to experience a unique with members of the community over the two years of my study.
than ethnic ethos (Patillo 2007; McKinnish et al. 2009). While I In this section I will first outline three perspectives: first that of
am defining gentrifiers in this paper as white to reflect how most of white gentrifiers I label as social preservationists, explaining why
my interview respondents defined gentrifiers and to show certain they fit into this category, how this influences their feelings about
patterns, it is important to keep in mind that the assumption that rebranding the neighborhood as Boston’s Latin Quarter, and how
only white residents are gentrifying HJS is an oversimplification2. this reflects how they define “authenticity”; next, that of gentrifiers
Although the categories are imperfect, I will treat long-term whom I define as social homesteaders, showing how they utilize a
Latino residents and business owners (more than 15 years3) as what place-based rather than people-based definition of authenticity; and
Brown-Saracino calls “authentic old-timers,” and white residents finally that of the Latino residents, demonstrating how their image
who are either wealthy or recent (have lived in the neighborhood of authenticity differs from that of the white gentrifiers.
less than 15 years ) as gentrifiers. I identified 12 people who are old-
timer Latinos and 12 who are gentrifiers—white, middle class, fairly Gentrifiers: white social preservationists
recent inhabitants of HJS. These 12 gentrifiers were divided in their The four gentrifiers who strongly supported the rebranding of
support of Boston’s Latin Quarter: four of them strongly supported HJS as Boston’s Latin Quarter were all highly representative of
Sociology
the name, five were clearly against the idea, and three were ambiva- Brown-Saracino’s definition of social preservationists: they see
lent. While this group of residents is fairly socioeconomically and Latinos as authentic old-timers and seek to preserve them through
politically diverse, those who support Boston’s Latin Quarter have symbolic, political, and private practices.
more characteristics of Brown-Saracino’s (2009, 2007, 2004) social
preservationists than did those who opposed the rebranding. On the Orientation toward the neighborhood
other hand, those who were against the rebranding effort seemed to Congruent with Brown-Saracino’s (2009, 2007, 2004) descrip-
fall more into her category of social homesteader. In my interviews tion of social preservationists, these white residents did not want
nobody appeared to fall into the pioneer category—unapologeti- to live in a gentrified, homogenized place. While they understand
cally supporting the displacement of working-class residents and that their own presence in HJS could result in this scenario, they
often motivated by profits. While the absence of this ideology in see the preservation of the Latino residents as an opportunity to
my interviews does not mean that it is not at all present among prevent it. Sandra, the resident who most clearly portrays the social
gentrifiers in the neighborhood, it does support Brown-Saracino’s preservationist ideology, explains:
finding that this ideology is less prevalent than earlier gentrification
scholars made it appear. I really moved to Hyde Jackson Square because it was not
gentrified. I love living in Hyde Square because of that reason,
and that’s the fear that I have…And it’s a little strange saying that
Findings coming from my background. You could look at it as well, I’m
kind of part of that gentrification, in essence. But I moved here
How people define place, and who they feel has a legitimate right with full embracing of being in this Latin community and taking
to do so, depends on many factors. When imagining Boston’s Latin it for what it is, not trying to change it. Being part of what’s here,
Quarter, many white gentrifiers worry about the current residents going down the street, partaking in a few sentences of Spanish
who are threatened by gentrification; about the businesses that or the smells, the feel. It almost feels like I’m in Mexico, and
might have to shut their doors if they do not find sources of revenue; I’m just going about 200 steps out my door, which is so great.
and about how they, as white gentrifiers, would fit in. They worry Working with the tailor down the street and trying to com-
about how to preserve the neighborhood —to insulate it from the municate with him on how to do alterations, looking up words
destructive forces of gentrification that would destroy the authentic in the dictionary to help my communication with him. I find
Latino flavor of HJS. all of that perfect, and I don’t want that to change. (47-year-old
However, some of the Latino merchants and residents see things white woman, resident)
differently. They understand that their children will be culturally
different from them. They understand that the neighborhood will Sandra likes living among Latinos and feeling like a tourist in her
not be the same tomorrow as it is today. For these Latinos, being own neighborhood, her own country. Like the other gentrifiers
defined as somehow more authentic by whites means imagining their who support Boston’s Latin Quarter, she makes an effort to shop
culture as stuck in time. For younger Latinos who are assimilating locally and support the mom-and-pop businesses in HJS. She also
and changing, this authentic culture is already a memory. recognizes that as a white person her views on gentrification are
somewhat hypocritical because she is in many respects a gentrifier.
2. In reality both white and Latino populations in HJS are socioeconomically However, she does not see herself as the stereotypical gentrifier,
diverse. The Latino population is not equally susceptible to gentrification. Some who does not care about the Latinos in the community. Instead,
of the Latino people to whom I spoke were homeowners, comfortably middle- she imagines herself as someone who cares deeply about the com-
class, and well-educated. These Latinos could be as much of a threat to the older
working-class Latino community as non-Latinos. The same distinction could be munity and actively tries to engage with the Latinos. She defines
made in the white population. Some are low income and could be displaced by Latinos as the legitimate members of the community and states
increased gentrification. Despite this diversity, during interviews it became clear that her goals are to not “change” that.
that respondents saw the white population as the gentrifying population. Perhaps
this is simply a conflation of race and class, or perhaps it is because the white pop- This ideology is clearly reflected in these gentrifiers’ reasons for
ulation is changing the cultural fabric of the district—demanding coffee shops wanting to live in the neighborhood. Kim, for example, says that
and organic food aisles rather than small bodegas and Latino owned restaurants. one of the reasons she came and has stayed in HJS is because she
3. While 15 is admittedly an arbitrary number, it does place these newcom-
ers as having moved to HJS sometime in or after the 1990s, which is when many really loves the Latino restaurants in the district. However, it was not
interviewees felt the process of gentrification in HJS began. only the food that attracted her, but the culture in the restaurants
www.thurj.org 85
themselves. In her words: it, really. It was fantastic. Then you get your little things, like, too
much parking, those nitpicky things that go on with people. I
They’re all amazing staples of this neighborhood. It brings think they should put as much parking as they can down there
people together. I’ve always had an appreciation for Latin Ameri- underneath those buildings. My neighbor is like, “No. If they
can families and their unity. I feel like this is a—even for single put more parking than they need, then we’re gonna have more
people, this is a very family-oriented neighborhood. So even if people.” Well, the businesses need people.
your family is not literally here, you still feel like you’re part of
a family, and that’s really kind of what I think of. (32-year-old Sandra, as a social preservationist, does not understand why other
white woman, resident) residents in the neighborhood would oppose affordable housing for
the parking that comes with it. In her eyes the parking will help
Although she is white, she enjoys living in a neighborhood with so the Latino businesses that are the backbone of the neighborhood
many Latinos because of their family values and welcoming atti- she wants to preserve.
tudes. These values mesh with hers and allow her to feel as though It is not terribly surprising that these same residents who fulfill
Sociology
she is part of a tight-knit community. This is such a large part of the social preservationist ideology are also the ones who support
her attraction to the community that she goes so far as to say that the project of Boston’s Latin Quarter. Boston’s Latin Quarter can
she would move out of the neighborhood if this family feel that be interpreted as both a form of political and symbolic preserva-
Latinos create went away. tion. It is political in the sense that the Main Streets organizational
The other residents who support the idea of Boston’s Latin Quar- agenda is connected to the city of Boston. Therefore, this rebrand-
ter expressed similar beliefs. Amanda mentions that beyond the ing plan gives political recognition to the Latino businesses in the
affordability of the neighborhood, she is attracted to the diversity, district and bestows a legitimate right to define place in HJS. It
saying: is symbolic in the sense that the businesses in the district are in
many ways the face of the neighborhood and influence how people
My child is gonna grow up having all this be normal. I feel see and understand their adjoining residential neighborhood. If
like where I grew up, in the middle of the woods, essentially, the commercial district stays in the hands of the Latino business
everything was a culture shock from there. He’s gonna grow up owners, then the neighborhood will retain a Latino identity even
hearing multi-languages, seeing and hearing and smelling things if the residential population becomes less Latino. In this sense, the
that are different from what we might do at our own house…I businesses themselves become symbolic replacements of Latinos
feel like that variety and just being able to eat different kinds of in the neighborhood. Even more, the advertising campaign meant
Spanish food I think is just really unique. It’s something that to support this neighborhood will drive this symbolic representa-
you’re just not gonna find in a lot of different neighborhoods. tion: Latino style festivals and events, murals, street signs, and
Everybody always has their favorite plantain spot, their favorite so on. These will all reinforce the impression that this is a Latino
this or that. (33-year-old white woman, resident, board member) neighborhood.
When I asked these residents if they felt the Boston’s Latin Quar-
For Amanda, the diversity gives the neighborhood its value. She ter name made sense, they all responded yes, that they felt that the
wants her child to understand cultures different from her own. name properly described the neighborhood, and more specifically
Through her cohabitation in this space, Amanda sees an opportu- the business district. When I asked what they understood as the
nity to give her son a life different from what she had growing up, motivation for redefining the commercial district as Boston’s Latin
shaped by the Latino culture. If Latinos disappear in the neighbor- Quarter, these residents often identified the preservation of Latinos
hood, this desirable aspect will also disappear. as a principal reason. It is important to note that these residents
did not see the rebranding effort as the only method of preserv-
Rebranding as preserving the authentic ing Latinos in the neighborhood. They also supported affordable
Based on this strong desire to maintain the current atmosphere housing and rent controls for the businesses as measures that would
of the neighborhood, these residents participate in efforts they feel help slow gentrification.
would help preserve the Latino culture here. In line with Brown-
Saracino’s (2009, 2007, 2004) definition, these social preservationists Social preservationists and authenticity
participate in private practices that they feel support local commu- How do the social preservationists use authenticity? As
nity, including shopping locally and making personal connections Brown-Saracino describes in her work (2009, 2007, 2004), social
with Latino neighbors and business owners. Amanda and Sandra preservationists define authenticity in terms of old-timers. Accord-
also participate in more political ways as well. Amanda (a HJSMS ingly, these residents define Latinos as the authentic inhabitants of
board member) serves on another local board in support of build- HJS. They see themselves as guests without the same moral rights
ing affordable housing in the neighborhood, which she hopes will to live here. This ideology motivates them to do things that they
slow down the process of gentrification. Sandra similarly takes believe will prevent displacement of the community’s Latinos.
part in other efforts that help support Latinos; in describing one First, these white social preservationists do not view white people
non-profit’s efforts to build affordable housing on the site of an like themselves as legitimate members of the neighborhood. At one
abandoned church she says: point in the interview Amanda articulates this feeling, comparing
HJS to the North End, the now highly gentrified Italian neighbor-
I’ve never seen something work so incredible as that. Reach hood of Boston:
out to the community, keeping people informed on what’s going
on, and be constant about it. I’ve never experienced anything like I feel like people who live there who weren’t Italian, it felt
like—I would imagine, they would say, “I live in an Italian neigh- residents also benefit from this plan. Through their support of the
borhood, this is the flavor of it, this is the culture, and I took rebranding efforts they can better justify themselves as not the
advantage of this, it was great. It was wonderful to be able to live kind of gentrifiers who simply try to invade and push out Latino
in a community like that.” But I don’t think that anybody who residents. Furthermore, by actively supporting the preservation of
was not Italian would say, “I’m from the North End.” They would Latino people, they define themselves as white. The definition of a
say, “I live in the North End.” I feel like it’s different. I can’t after Latino place that is distinct from other parts of the city reinforces
nine years saying I’m from Hyde Jackson Square. the concept of Latino: a people who have their own non-white socio-
cultural practices. The mirror image of this is that the creation of
While Amanda lives, works and raises her family in HJS, she does Boston’s Latin Quarter simultaneously maintains whiteness as
not see herself as a legitimate, authentic community resident. Just as different from this image. Also, if Latino people assimilated with
non-Italians cannot be part of the North End, non-Latinos cannot the white population, or moved elsewhere, these social preserva-
be true residents of HJS. They can only enjoy the neighborhood as tionists could no longer benefit from living in this multicultural
a Latino place. neighborhood that they so enjoy.
Sociology
When I asked the social preservationists whether the Latin
Quarter could be authentic, most expressed concern. They realize Gentrifiers: white social homesteaders
Boston’s Latin Quarter could become “theme-park”-like. How- In contrast to the white residential population who support Bos-
ever, when pressed further they still seemed to feel that rebranding ton’s Latin Quarter, non-supporters were much more reflective of
was a good path to follow. Amanda points out that HJS, not being Brown-Saracino’s social homesteaders, those who like the diversity
at the center of town and still largely working class, needs active of the neighborhood but also believe that they have as much of a
promotion to get people to visit, and that for the ultimate good of right to establish roots in the neighborhood as the Latinos.
the business district, and the Latinos who run it, this promotion
is necessary. Another resident, Lesley, pointed out that with the Orientation toward the neighborhood
affordable housing being built in the neighborhood she does not These residents moved into the neighborhood to build a home
see this as becoming a big issue. However, the businesses, since they for themselves and their families. While they appreciate the Latino
are not subject to rent controls, are vulnerable, and ultimately need identity of the neighborhood, this was, at most, a secondary reason
the support of Main Street if they hope to survive. for moving here. Instead, this group came to live with significant
Sandra stated that because branding the area as Boston’s Latin others or family members or they came because the neighborhood
Quarter is a business plan, she sees authenticity as a problem. How- offered them a chance to buy an affordable home. While this group
ever, she encourages the local businesses not to change. When asked was not necessarily any less educated or less liberal than the social
if she felt that visitors would find the businesses accessible, she says: preservationists, they simply had different priorities.
Another interesting finding is that this group seemed to par-
I would like to hope that they’re accessible to everybody. I’ve ticularly appreciate the diversity of the neighborhood, rather than
never had any ill experiences with any of those vendors down simply the Latino identity. These residents were attracted by the fact
there. They’ve all been fantastic. They have helped me with my that HJS is known for being progressive and liberal, open to gay
Spanish. I have helped them with their English. Not everybody’s men, lesbians, and non-white residents. For example, when I asked
like me, though. That’s the challenge. I can see some people com- Mark what has kept him in the neighborhood so long, he explains:
ing from somewhere else and not being as able to enter the door.
Especially somebody that’s never been to Mexico, somebody Well, I like the diversity of it. I like the fact that there’s a strong
that doesn’t identify with any kind of Latina/Latino culture. component of liberal, progressive openness to the lifestyles, a
They might have a hard time, but you know what? That’s why general acceptance of gay people, same-sex marriage. I like the
it’s there. When they’re ready, it’s there waitin’ for ‘em, right? fact that it’s got a thriving downtown. We have a couple friends
that live in JP now. I like the fact that there seems to be a sense
While she does readily admit that some people might not be as of community. (52-year-old white man, resident)
comfortable going to these businesses as she is, she does not think
that the businesses should become more accommodating. They While Mark certainly recognizes that there are a lot of Latino people
should wait for the kind of people who are okay with being in a within the neighborhood, and later will say that it is fun to live in a
“foreign” setting. In this way authenticity can still be maintained, place that is so diverse, Latinos are not the first group he mentions.
and the businesses can benefit from increased visitors. Similarly, in Brian’s description of what he feels attracts people, there
Whether or not these residents’ predictions about how best to is a nod to diversity, but no mention of Latino people or culture.
maintain the authentic “other” are accurate, this ideology is inter- He explains what he likes:
esting in itself. These white gentrifiers enjoy living in a diverse
neighborhood with Latino old-timers, and they see Boston’s The greenness of it, the fact that there’s a lot of parks here,
Latin Quarter as a method to preserve the Latino identity, and and the pond, surrounded by a park, and the fact that it’s very
to recognize the Latino presence in the neighborhood. Following low-crime, at least from what I see…. There’s a lot less—it seems
Brown-Saracino’s description of social preservationists, they con- like there’s a lot of homeowners here, but it’s not like Beacon
nect authenticity to these ethnic old-timers in the neighborhood Hill, where they’re extremely affluent. I think there’s a lot of
and work to preserve the neighborhood’s authenticity through the first-time homebuyers here in this community, and a lot of ‘em
preservation of these people. However, this rebranding plan does live in the houses that they own. They’re not rental, they’re not
not only impact the Latino residents and business owners. White bought to rent out and make money off of, so people really enjoy
www.thurj.org 87
their houses and do a good job of landscaping and gardening Rebranding as exclusion
and stuff like that and really try to beautify their neighborhood Unlike the social preservationists, this group felt that the name
from their doorstep outward.…There’s a lot less trash on the Boston’s Latin Quarter was exclusionary; not surprising when these
streets than in some of the other neighborhoods in Boston, and social homesteaders already feel somewhat resented within the
a general sense of racial equality or whatever….I think there’s neighborhood. For example, Chris explains:
such a diverse population that everybody feels like they belong
in JP. Obviously, sexual orientation in this community isn’t really My wife and I were talking about it last night…We live here,
an issue, and that’s kind of really soothing or whatever…I think we appreciate Hispanic culture. I’ve been to Brazil, she’s been
everybody enjoys the fact that everybody is pretty free to wave to the Dominican Republic. I’ve worked with Hispanics. I’ve
their freak flag, no matter what that flag is. You don’t really hear employed Hispanics. My wife and I both speak quite a bit of
too many people givin’ anybody any grief over it. (40-year-old Spanish. I appreciate siestas [laughs] and that whole thing. But
white man, resident, business owner) I guess we don’t—I guess we won’t feel comfortable where—we
feel like there’s a lot of Latin pride around here and this might
Sociology
While these definitions show that residents have diverse reasons for push it a little further and make us not feel welcome, basically.
wanting to move to HJS, it also highlights why these people may be (39-year-old white man, resident)
less concerned about gentrification and the preservation of Latinos.
This group likes that HJS is not full of WASPs and yuppies; the His wife, Tracy, later adds that she feels that the name would not be
diversity they see is not a diversity that will be negatively impacted good for the community, because it might deter other non-Latinos
by their own presence. For example, HJS is more recently a home from moving in. She points out that while they were looking for
to a lesbian population, which is mentioned by both Mark and a diverse neighborhood to live in, they did not move into China-
Brian. Since they add to the diversity and progressive feel of HJS, town, because they did not want to be the only Anglo people in a
this group is at less risk of displacement due to gentrification. This neighborhood. While Chris and Tracy tried very hard to make sure
broadened definition of who belongs here to include groups that are I understood that they were not prejudiced toward Latino people,
generally more upwardly mobile arguably allows these gentrifiers they were threatened by the idea of living in an area that had so
to be more comfortable with their own role in the neighborhood. much Latino pride that they would feel unwelcome in it. They are
They are simply people who add to the diversity. not comfortable with the idea of being the only white faces within a
Another interesting finding within the social homesteaders is neighborhood and would not have chosen HJS if it had been called
that three out of the five people in this group expressed that they Boston’s Latin Quarter when they moved here six years ago. While
felt that Latinos in the neighborhood resented their presence. For they argued that they were not gentrifiers themselves, they would
example, Mark explains: ultimately like to see more white people move in. They want to
feel part of a community of diverse people, rather than cultural
I don’t feel as at home in Hyde Square…I like it, I enjoy it, outsiders living amongst people with whom they do not identify.
but I don’t connect in the same way. I’ll go into a convenience Julianne, who did not feel at all resented within the community,
store to pick up some milk and it’ll be friendly, but there’s a believes that Boston’s Latin Quarter would be exclusive for a very
sense…whether it’s because of the language barrier or because different reason: it would not have enough diversity. She explains,
of the history of gentrification in the neighborhood, there’s a “I’m lazy. I prefer to have a lot of variety near my house, instead of
real feeling that it takes a long time for an Anglo to feel welcome having to feel like I should go really far away for specific things.”
and not a lot of eye contact happens on the street. There’s a lot She would like to see Indian restaurants and sushi places, rather
of distancing, whether it’s us that does it or them that do it. My than Latino restaurant after Latino restaurant. While she admits
perception is that we’re more outgoing and smiling than we’re this is a shallow reason of her own, it is not a terribly unreasonable
getting from the Latino community. one. People like having a variety of places near where they live. It
is convenient. However, this response would not necessarily come
Unlike the social preservationists, Mark does not describe Latino from a social preservationist. Julianne is expressing that she wants
people as warm or friendly. While Sandra saw interactions with the community to serve her own needs, perhaps over the needs of
Latinos as an opportunity to practice her Spanish, and Amanda the old-timer Latinos4.
expressed excitement that her son would grow up accustomed to Homesteaders, authenticity, and Boston’s Latin Quarter. The
diversity, Mark feels like a cultural outsider, excluded in his own other argument that is prevalent among social homesteaders is
neighborhood. He feels he cannot engage in or fully become part that Boston’s Latin Quarter feels artificial. This complicates Brown-
of the community. He feels unwanted by the Latino community. Saracino’s typology—showing that the social preservationists are
While he understands that there might be some resentment towards not the only gentrifiers primarily concerned about authenticity.
him because he is viewed as a gentrifier, he does not see himself For example, when I asked Julianne if she thinks the name made
this way. The three people who described feeling resented also were sense for the neighborhood, she compares it to the gentrified Ital-
quick to point out that they came to the neighborhood because it ian North End:
was so affordable. They do not see themselves as part of the gentri-
fication. Whether or not this is actually the case, they felt a need to It seems like it tries to hold something in time that is artificial.
justify their right to live here. These are not the expressions of social
pioneers, who would be unconcerned by feelings of resentment or
4. Interestingly, a couple of the Latino people I interviewed expressed this
outsider status. Instead, these are simply people who want to feel same idea that they would like to see more variety of restaurants in their own
more at home in HJS. neighborhood beyond the Latino places.
To reiterate, just the way the North End feels to me now. It does the neighborhood. However, when one considers the fact that these
not have the stores that we used to shop in. There aren’t any residents use a broadened definition of diversity that allows them
stores. There are boutiques, and there are restaurants, but you to include themselves as legitimate members of the community,
don’t shop there. You don’t get your groceries. You don’t have these ideological decisions make more sense. Even more, mirror-
your chickens and your lamb hanging in the storefronts and the ing Zukin’s (2010) argument, these gentrifiers are more concerned
bags of coffee and herbs and stuff. It just doesn’t exist any more. about maintaining an authentic place rather than an authentic
(48-year-old white woman, resident) people. This adds a dimension to Brown-Saracino’s work showing
that social-homesteaders’ ideological stance towards preservation
While Julianne and the others who did not support the Latin Quar- is still rooted in authenticity, but not authenticity grounded in
ter enjoyed aspects of living in a diverse neighborhood, they are authentic old-timers.
more concerned about living in an authentic place. Therefore, she
proposes that rather than market the neighborhood and turn it into Latino perspectives
a tourist trap that does not service the people who live there, the While Latinos are just as torn about their support of the Latin
Sociology
community should foster authenticity in other ways. For example, Quarter as the white population, they did not talk about their con-
she says that some Dominican ball-players for the Red-Sox come cerns surrounding authenticity in the same ways.
here for haircuts, which could be a source of pride for HJS and a
way to foster the Latino identity of the place. New Latinos
Similarly, Mark points out that he would be more comfortable Only two of the Latinos I spoke with were highly concerned about
in seeing the non-profits do educational programs teaching about the commercialization of the Latino businesses, and both of them
Latino cultures, rather than a promotional campaign that will bring were younger, well-educated newcomers to the community who in
in non-community members. He explains: some ways are more similar to the gentrifiers than the older Latino
immigrant stock. While these two people stood out from the typical
I don’t know. I think if you’re preserving culture, it’s a tricky Latino attitudes toward Boston’s Latin Quarter, their opinions and
thing. Culture is ever-changing and always being influenced voices are just as important as those of the older residents.
by other cultures. If the mechanism to preserve a culture is to Antonio says that he will never use the name Boston’s Latin
actually make it more open to outside culture, then what you’re Quarter. This is partially because the name does not define him;
doing is, you’re really creating a museum. And …that doesn’t he makes it clear that this marketing plan is not meant for Latinos:
make sense. But I think you preserve culture not through what
kind of stores are there or what language it’s in—although I’m It’s in English, for one. It automatically takes us out of the
sure that helps sustain the feeling of community, but it really equation. So who is it for? It pushes to me further from what
has to do with organizations that bring people together to teach we’re fighting for as far as gentrification is concerned. I will draw
them about their culture, their heritage, like spontaneous cel- a parallel to youth development, which is, a young person who
ebrations. Not that that’s purely a Latino thing, but there seems is clear about their identity and their history and their culture
to be a big institution there. Maybe that brings people together. is better poised to succeed as an adult. I would say that can be
Church brings people together to create a sense of community. true to districts also. What has made Hyde Jackson Square this
I think that’s where the preservation that’s not museum-like whole time special is the people that live and work in it, so I
comes into effect. That’s just my opinion. think that that should be reflected in the name. Who’s Latin? I
don’t know what that is. I don’t ever consider myself Latin. And
Mark feels that marketing Latino culture to outsiders is not the I see a lot of Caribbean here. There are some South and Central
best course of action because it turns their culture into a museum American also… I wonder if many people identify themselves
and does not build community. In some ways, he is expressing a as “Latin.” Latinos. I’m sure that Latino Quarter doesn’t make a
concept that the Latino residents very much agree with: culture is lot of sense. (35-year-old Latino man, resident, youth-organizer)
not static. He sees Boston’s Latin Quarter as something that will
be inflexible and will destroy the feeling of the neighborhood as an In many ways the name Boston’s Latin Quarter is a representation of
authentic and strong community, making it a place for outsiders to an abstract concept. While this issue of whether the Latin Quarter
come see a manufactured image of Latinos. properly describes the neighborhood might seem like a debate of
While Brown-Saracino stresses that social preservationists are semantics, it has important implications. The idea of Latinos, or
concerned with living in authentic places surrounded by authentic Latin people, is very much a constructed category. The term Latino
old-timers, it seems that social homesteaders are equally concerned assumes that people from South and Central America, as well as the
with authenticity. However, they define authenticity in a way that Hispanic Caribbean, are largely similar. As Antonio points out, if
gives them, as legitimate members of the community, a right to live the name itself is not how Latinos living in the community imagine
in their image of an “authentic” community. In other words they themselves, then who is Boston’s Latin Quarter for? Is the primary
have a right to live in a place that does not feel like a tourist trap, target audience for such a plan non-Latinos who are attracted by
some Latino version of Disneyland. the “exotic” and “trendy” image they have of the community? Is it,
It seems ironic that social homesteaders—who expressed so as Antonio describes, going to result in whites “coming to stare at
much concern about defining authenticity of place and who for the the brown people?”
most part believe that Boston’s Latin Quarter will result in a com- Emilia also worried that this plan would create inauthentic rep-
mercialized, inauthentic representation of Latino people—were not resentations having nothing to do with how Latinos actually see
terribly concerned about actually preserving the Latino presence in themselves. Like Antonio, Emilia does not want to see Latinos
www.thurj.org 89
reduced to commodities for white consumption. She likes shop- The demographic change is seen as natural, rather than something
ping in the stores and the down-home feel of the neighborhood, to be mourned.
and she cannot imagine that tourists would be attracted to these
places. Therefore, she envisions that in Boston’s Latin Quarter the Old-timers who support Boston’s Latin Quarter
businesses would have to change. For her, this would be “terrifying” There are also a number of Latino business owners and residents
as it would mean that HJS would “lose its soul.” who do support the rebranding of Boston’s Latin Quarter. Predict-
Prior to my research, these are the reactions I hypothesized I ably some business owners are only motivated by the potential
would get from Latinos based on the extensive literature surround- economic benefit to them. But other Latinos have more symbolic
ing the term “Latino” that is often not how those who fall underneath reasons for supporting the idea. What is most interesting about
its umbrella see or describe themselves (Gimenez 1996; Dávila 2000, this symbolic support is that these Latinos are not concerned with
Oboler 1998). I similarly was worried that the name covered up keeping the area an “authentic” Latin space that caters primarily to
heterogeneity among the Latino population and was based on a Latinos. Instead, they are interested in gaining recognition.
manufactured, stereotyped image of Latinos that ultimately was José does not think that businesses necessarily have to change,
Sociology
meant to attract outsiders rather than Latino people. Therefore, I or become less Latino, to accommodate white populations. He
was somewhat surprised that among the older, long-term Latinos compares the neighborhood to Chinatown, where outsiders come
there was very little anger or worry that the neighborhood would in understanding that there will be language barriers and cultural
become inauthentic or that the name was imprecise. For some who differences and simply get past them. However, he also feels that as
have spent much of their lives as marginalized members of the the demographics change the business district needs to be willing
Boston community, even an inauthentic Latin Quarter has value. to change in order to stay afloat. While he makes these arguments,
he also explains that authenticity is not his primary concern. The
Old-timers who do not identify with Boston’s Latin Quarter main benefit he sees from Boston’s Latin Quarter is that it will serve
Not all of the old-time Latino residents support the idea of Bos- as a reminder for the next generation. Even if HJS becomes less
ton’s Latin Quarter. However, this was not because they felt it would authentic and less Latino residentially, he feels the most important
make the neighborhood inauthentic. They simply feel that it is not reason to maintain this area as a Latin space is to remind the next
an accurate description of the community. For example, María, a generation about their culture, saying:
restaurant owner, claims that the name feels inappropriate because
over the last few years many more “Americans” were moving in. I think today a lot of our children are more lost than ever as
Since white Anglo people are replacing the Latino population, it far as our own culture, and you have so many different influences
does not make sense to identify the neighborhood with a dying coming in, it’s really tough to say, “You know what? You can be
population. She explains that now her customers are almost all white open to some of these other cultures, but you definitely need
people. Unlike the white members of the community, María does to learn and keep on to our culture.” And I think by having a
not see gentrification as the sole cause of this change; she points out neighborhood like that, it at least helps. It’s not gonna solve the
that as Latinos begin to open businesses in other parts of the city, problem, but it at least helps. (35-year-old Latino man, resident,
such as East Boston, Latinos have fewer reasons to make a trip to business owner)
HJS. Furthermore, some Latinos have moved on to the suburbs and
warmer locations out of choice rather than because of displacement. For José, preserving an area as Boston’s Latin Quarter is not about
María’s argument is about authenticity, but she is defining creating an authentic space, but maintaining the image of Latinos.
authenticity differently once again: in terms of pure population While he sees assimilation among the third and fourth generations
changes rather than feelings about how culture is represented as inevitable, he sees Boston’s Latin Quarter as a symbolic repre-
within the community. This same issue concerned some of the sentation of the history of Latinos, reminding future generations
non-Latino residents, but not to the degree that they felt the name that their heritage is distinct and different.
was an inappropriate descriptor of the mostly Latino commercial José is not the only person to make this argument. Amado, who
district. However, for María it did not matter terribly that the busi- is on the board of HJSMS himself, admits that the rebranding effort
nesses themselves remained Latino. She has seen her own business is a generation too late and that it is an inauthentic representation
change because of the residential demographic shift. While the Lati- of the neighborhood. However, he disputes that authenticity ulti-
nos who used to eat at her restaurant would order larger meat plates mately was what the decision was about. For Amado, whose three
that had that special “Hispanic touch,” the white residents mostly children have forgotten their Spanish, the process of assimilation
order fast food items such as tacos and burritos, which she views as is not only inevitable but is also good. He explains that the next
evidence that the neighborhood is no longer really Latino. Another generations of Latinos will be more educated and more successful
major difference is that, unlike the white social preservationists, than his generation. He feels that it is silly to try and freeze the
she and the other Latinos who see the neighborhood becoming less neighborhood in time, because you cannot hope to reproduce the
Latino are not upset about it. As someone who already moved out past and fight the natural progression. He attests that over his own
of HJS, she seems to simply accept the fact that the Latino popula- lifetime his understanding of himself as a Dominican, a Latino, and
tion is moving elsewhere. Her tone expressed weariness with the a person of color has transformed. Like his self-identity, the iden-
neighborhood. She remembers when HJS was a dangerous place tity of the neighborhood will change, and cannot possibly remain
and is exhausted by the years of managing a business here. This is “authentically” Latino as it used to be. The assumption that Latino
not atypical. Other Latinos I spoke with were counting the days culture is something static is unrealistic. Despite this belief, he
until they could afford to move someplace warmer and quieter and argues that the name “does make sense.” saying, “I think it’s never
therefore could not care less about the impending gentrification. too late if you want to do something positive.” For him, this is a
way for Latinos to get political recognition, to be remembered as social distance and the authentic other allowed them to hold onto
active players in Boston’s history. While it may not be authentic, their identity as “good” white gentrifiers, open to other populations
and it may commodify Latinos, for him it will stand as a reminder and actively supporting them. For Latinos, the goal was more about
to his three children that they have a place in Boston’s past and are remembrance; they hoped to remind the next generation of Latinos
valued by the city. about their culture and the role of Latinos in shaping the city.
Conclusion References
Underlying the rebranding effort of Boston’s Latin Quarter is a Brown-Saracino, Japonica. 2009. A Neighborhood that Never Changes: Gen-
debate about the goals of redefining this place and about how this trification, Social Preservation, and the Search for Authenticity. Chicago,
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Sociology
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over place identity, particularly as gentrification plays out, and as City and Community 3(2): 135-156
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by trying to slow the process down through the preservation of Stefancic. New York: New York University Press.
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about gentrification by imagining themselves as legitimate members City. Chicago: University of Chicago Press.
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Quarter with the argument that this is not ultimately good for Small, Mario L. 2009. “‘How Many Cases Do I Need?’ On Science and the
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A comparison between the responses of the white gentrifiers Social Explorer. 2010. “2007 Census Tract Estimates, Suffolk County.” Retrieved
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www.thurj.org 91
Structure-function analysis of newly-

identified adamantylacetamide and
adamantanecarboxamide inhibitors of
Ebola and Lassa fever virus infection
Huy Nguyen ‘10
Harvard Medical School
Previous studies using high throughput screening identified an adamantylacetamide compound, 3.0, as a specific
inhibitor of the Ebola virus infection. Compound 3.0 acts on cells to prevent activation of the membrane fusion
activity of the EBOV glycoprotein. Initial chemical dissection of 3.0 activity identified a related adamantan-
ecarboxamide compound 3.3 that is a weak EBOV inhibitor, but strongly inhibits Lassa fever virus infection.
To identify the molecular basis for the anti-virus activity and specificity of this class of compounds, additional
comparative SAR studies have been performed. The strategy was to analyze the relative contribution of each
Chemical and
of the four structural groups—an adamantyl group, a methylene linker, an amino acid linker, and a benzylpi-
Physical Bio
perazine group to anti-viral activity. Synthetic schemes were devised and optimized for the creation of these
adamantylacetamide and adamantanecarboxamide derivatives, including adoption of the Katritzky reaction.
The derivatives were tested for antiviral function on a whole-cell assay using single cycle EBOV-GFP or LV-GFP
infection. It was found that none of the derivatives synthesized in this study had better antiviral activity than
the parent compounds 3.0 and 3.3, suggesting that the parent compounds interact with specific targets in cells.
Importantly, specific modifications of the benzylpiperazine group were identified that did not markedly reduce
anti-viral activity. These modifications provide the basis for synthesis of derivatives bearing photo-reactive and
fluorescent tags that can be used to probe cells to identify EBOV and Lassa fever virus host factors. In addition,
these studies inform future development of adamantanecarboxamides or adamantylacetamides as anti-viral drugs.
Introduction
hemorrhagic fever in humans as well as nonhuman primates. Char-
The entry of enveloped viruses into host cells requires the fusion acterized by severe internal bleeding, irregularities in coagulation,
of the viral membrane with the target-cell membrane. However, and hypovolemic shock, EBOV hemorrhagic fever is highly trans-
since biological membranes are naturally stable, membrane fusion missible and results in 40% to 90% lethality within one to two
generally requires a large source of energy. For type I viral mem- weeks [2]. There is currently no vaccine or treatment for EBOV
brane fusion, this energy derives from the free energy that is given hemorrhagic fever, which makes it a potentially acute public health
off by significant conformational changes in viral envelope glycopro- threat, especially in sub-Saharan Africa.
teins (Env) [1]. Even though the fusion of two bilayer membranes is
thermodynamically favorable, there is a high kinetic barrier which Search for EBOV host factors
prevents fusion from occurring spontaneously when the viral mem- Despite the difficulties of studying the highly pathogenic virus,
brane and the host cell membrane come into contact. This kinetic significant progress has been made in identifying the mechanism
barrier is overcome when free energy is liberated from the confor- by which EBOV spreads. Ebolaviruses are filamentous enveloped
mational changes of Env viral proteins [1]. viruses, and like many other enveloped viruses, they enter host
cells through either endocytosis or phagocytosis [3]. Following
Ebolavirus membrane fusion entry into the endocytic pathway, EBOV progresses through the
A constructive example by which we can study the viral fusion cycle of maturing endosomes until it is ready to fuse with the host
mechanism is the entry procedure of Ebolavirus (EBOV). Not all cell membrane and enter the cytoplasm [3].
cellular host factors which are essential for EBOV viral fusion have Ebolaviruses contain two virally-encoded glycoproteins, GP1 and
been identified, and further investigation of this phenomenon might GP2, which are both crucial for viral entry into a host cytoplasm.4
also elucidate other key components to the entry process. The two glycoproteins are products of the cleavage of the precursor
trimer GP0 by a furin-like endoprotease. Following cleavage, GP1
Ebolavirus background and GP2 remain linked by a disulfide bridge [5]. The surface-bound
Ebolavirus, a member of the family Filoviridae, is an emerg- protein GP1 contains a mucin domain, which is a highly N- and
ing infectious negative RNA-stranded virus which causes severe O-glycosylated region helping to enhance infection of target cells [6].
this low pH is required for the endosomal cathepsin L (CatL) and

cathepsin B (CatB) to cleave GP1 [12]. CatL and CatB are cysteine
proteases which convert GP1 from a 130 kDa species to a 18 kDa
and 17kDa form, respectively [12]. This cathepsin-cleaved GP1 has
been shown to be a necessary prerequisite for membrane fusion,
although it is not sufficient. Chandran et al. report that in addition to
the CatL/CatB cleavage of GP1, the additional step of removing the
GP1-18K region must be completed to expose GP2 and trigger fusion
[9]. The rare requirement of pH-activated cathepsins makes EBOV
different from most other pH-dependent viruses, whose viral GP
undergoes conformational changes leading to viral fusion directly
as a result of low pH [9]. Cathepsins are predominately found in
Figure 1. Anti-EBOV (ZdM), anti-LV, and anti-VSVG activity of Com- late endosomes and lysosomes with pH values at approximately
pound 3.0. Compound 3.0 is specific for inhibiting EBOV viral entry. 4.5-5.0, and this provides conclusive evidence that EBOV must be
transported into these intracellular compartments. Unfortunately,
the actual trafficking pathways involved are unknown.
GP2, a transmembrane protein, has been confirmed to be directly
involved in membrane fusion [7]. Anti-Ebola GP high-throughput screen
To identify inhibitors which block the interaction between GP1-
Unknown receptor for EBOV GP1 17K and the key missing host factor, colleagues in the Cunningham
The triggering signal for the EBOV GP1-GP2 trimer is unknown lab used the GFP-encoding vesicular stomatitis virus (VSV) GP as a
Chemical and
– specifically, it is not clear if there exists a classic receptor on the basis for a high-throughput assay on African green monkey kidney
Physical Bio
host cell which binds to intact GP1 [8]. Moreover, EBOV infects epithelial (Vero) cells. VSV particles expressing native VSV-G glyco-
a wide variety of cell types, unlike viruses such as HIV-1, which protein were used as a control for the pseudotyped VSV containing
only infect specific cell types. It has not been concluded if a high- the EBOV Zaire delta mucin (ZdM) GP on its surface. Over 50,000
affinity binding site exists for GP1, but since EBOV infects such a small molecules at 25 μM from existing small molecule libraries
wide range of cell types, there may be more than just a single high were screened. Seven EBOV inhibitors were identified as potent
affinity surface receptor for GP1 on the cell surface. (IC50 < 1 μM), specific, and non-toxic.1
Cathepsin cleavage of GP1 is required for fusion The adamantylacetamide hit, “Compound 3.0,” is a specific EBOV
Since inhibitors of endosomal acidification have been shown to inhibitor
block EBOV entry, it has been confirmed that EBOV uses a pH- Of these seven hits, the adamantylacetamide “Compound 3.0”
dependent entry mechanism [9]. The acidic pH leads to an essential
destabilization and rearrangement of the GP2 structure [10,11]. 1. Structures of Compounds 1.0, 2.0, 4.0, 5.0, 6.0 and 7.0 are not included in
Additionally, this study.
Figure 2. Compound 3.0 and Compound 3.3: Inhibition on EBOV and LV. Compound 3.0 is specific for EBOV inhibition while Compound 3.3 is specific
for LV inhibition.
www.thurj.org 93
Figure 3. (3a) Structure of Compound 3.0 includes four arbitrarily assigned

groups: Adamantane, methylene linker, amino acid linker, and benzylpipera-
zine. (3b) Compound 3.3 is missing the methylene linker and has a substitu-
tion on the benzylpiperazine moiety.
was chosen as the focus of this study for several reasons. First, the two compounds have astonishingly different viral specificities.
Compound 3.0 is specific for EBOV and does not block VSV or This suggests that the Compound 3.0 pharmacophore was active
Lassa fever virus (LV) from the Arenaviridae family, which also against more than one virus and that there had to be some common
Chemical and
possesses a type I envelope glycoprotein (Figure 1). LV has been property with how the cell interacts with EBOV and LV. Since the
Physical Bio
shown to require a very low pH environment (<5.2), which sug- Compound 3.0 pharmacophore could hold the key to deciphering
gests that it also localizes to the same late endosome or lysosomal the mechanisms by which specific viruses infect host cells, a SAR
compartments, which contain cathepsins. Thus, it is unlikely that analysis of Compound 3.0’s structure was proposed.
Compound 3.0 is a general cathepsin inhibitor and more likely that
it is a specific EBOV entry mechanism inhibitor. Compound 3.0 and Compound 3.3 are specific
Second, Compound 3.0 has been shown in private communica- The significance of the finding of Compound 3.3 is illustrated by
tion to work on the cell and not the virus. EBOV infection was not another observation. Since EBOV and LV could both be inhibited
inhibited by preincubation with Compound 3.0. While this does by the lysosomotropic agent ammonium chloride (NH4Cl) [1], that
not rule our a rapid reversible off rate of Compound 3.0 from virus there was a common step to their respective viral fusions. Since
particles, the experiment suggests that the compound works on the Compound 3.0 and Compound 3.3 do not follow the indiscrimi-
cell, possibly inhibiting a cellular host factor. Third, Compound nate inhibitory pattern of NH4Cl, they are not general inhibitors of
3.0 inhibits the post-cathepsin, cleaved form of EBOV-GP1. If the viral entry but rather specific inhibitors. Therefore, the Compound
virus was predigested to remove the glycan mucin cap, the resulting 3.0 series must have specific antiviral activity covering more than
GP1-17K particle is still blocked by Compound 3.0. one virus, which makes them highly desirable as tools to study
specific viral fusion. Taken together, these findings led to the work-
The adamantanecarboxamide “Compound 3.3” is a specific LV ing hypothesis that EBOV and LV use overlapping host proteins
inhibitor or pathways via similar binding sites to gain entry and map to the
The fourth and most interesting reason that Compound 3.0 was GP1 clamping domain of EBOV.
chosen to be the subject of this study comes from a structure-activity
relationship (SAR) study of the compound. Several small molecules Structure of Compound 3.0 and 3.3
structurally similar to Compound 3.0 were commercially obtained Close scrutiny of the structure of Compound 3.0 reveals four
and tested for anti-EBOV and anti-LV activity, 2 using VSV as a possible structural elements which could be varied for a thorough
control. This SAR included data against LV infection since LV is not SAR analysis (Figure 3a). As shown below, Compound 3.0 possesses
very similar to EBOV, and by comparing the compounds’ effects an adamantyl group, a methylene linker, an amino acid linker (in
against LV infection as well, universal virus inhibitors blocking this case, glycine), and a benzylpiperazine moiety. Compound 3.3
some common process could be identified versus compounds which (Figure 3b) differs from Compound 3.0 in only two regions: the
were more selective for either EBOV or LV inhibition. None of these loss of the methylene group adjacent to the adamantane and the
Compound 3.0 derivatives proved to have any significant anti- addition of a phenyl ring at the benzylpiperazine end.
EBOV activity, but one, the adamantanecarboxamide “Compound The addition of the phenyl ring at the benzylpiperazine end on
3.3,” was remarkably found to significantly inhibit LV infection Compound 3.3 was suspected to be the primary contributor to this
while allowing EBOV infection (Figure 2). The antiviral patterns of significant change in viral specificity. A SAR study on the effects
Compound 3.3 are an unexpected yet extremely intriguing result. of various substitutions on Compound 3.0 was proposed with the
While the structural differences between Compound 3.0 and Com- hopes that it might lead to a better understanding of what kind
pound 3.3 (a benzyl group and a methylene linker) are minimal, of functional groups provided specificity against viral infection,
specifically between EBOV and LV infection.
2. Structures of derivatives 3.1, 3.2, 3.4, 3.5, 3.6, and 3.7 are not included in To better understand the post-cathepsin step by which EBOV and
this study. LV infect host cells, it is important to identify the targets to which
Compound 3.0 and Compound 3.3 bind. To elucidate the particular derivatives of Compound 3.0 with a diversely functionalized ben-
properties of Compound 3.0 and Compound 3.3 which confer the zylpiperazine region, a different synthetic route was preferred that
specific activity against EBOV and LV, a chemical dissection of would effect the requisite benzylation in the last step. The new
the compounds was first performed by systematically altering the synthetic scheme begins with a condensation reaction of 1-Cbz-
four distinct groups outlined in Figure 4 to create two families of piperazine with the amino acid linker, followed by Boc deprotection,
derivatives, one for Compound 3.0 and one for Compound 3.3. A coupling with the adamantyl moiety, Cbz deprotection, and finally
strategy for the rapid synthesis of Compound 3.0, 3.3, and several introduction of the substituents on the piperazine via reductive
informative derivatives for each compound was developed. Next, a amination with 31 different benzaldehydes. Products B1-B31 were
structure-activity relationship study was performed by testing the formed (Table 3).
derivatives’ antiviral activities via a biological assay. Based on the
results, conclusions were drawn about which parts of the molecules Adamantane
were important in conferring specific antiviral activity. The necessity of the adamantyl group in blocking antiviral activ-
ity was tested. Since the stock of 1-benzylpiperazine, a necessary
component in the synthetic route outlined above to synthesize
Results Compound 3.0, was limited, the commercially available 1-diphe-
nylmethylpiperazine was used. BOP coupling was used to react
Boc-Glycine with 1-diphenylmethylpiperazine to form an interme-
Specific aim 1: Synthesis of informative derivatives of diate, which was then deprotected with TFA and condensed with
Compound 3.0 and 3.3 adamantane-1-acetyl chloride and 2-cyclohexyl acetyl chloride to
produce products A1 and A2 (Table 5).
Synthesis of Compound 3.0 derivatives
Chemical and
The following reaction scheme was originally developed to syn- Synthesis of Compound 3.3 derivatives
Physical Bio
thesize Compound 3.0. There are two differences between Compound 3.0 and Compound
3.3. The first is while Compound 3.0 is an adamantylacetamide,
Compound 3.3 is an adamantanecarboxamide. The second dif-
ference between the two compounds lies in the benzylpiperazine
region of the molecules, where only Compound 3.3 has a phenyl
Scheme 1. Originally developed reaction scheme to synthesize Compound group substituted on the benzylic position. One, or both, of these
3.0, starting from Boc-protected (both L and D) amino acids differences must somehow confer specific resistance to Ebola and
Lassa infection. Here, substitutions were introduced to the ben-
Methylene linker zylpiperazine region since from the synthesis of Compound 3.0
First, a transformation of adamantane-1-acetic acid to adaman- derivatives, variations in the benzylpiperazine ring offered the most
tane-1-acetyl chloride with SOCl2 was performed under a reflux data on what substituents could inhibit viral activity.
condition. Similarly, adamantane-1-carbonyl chloride was synthe-
sized from the corresponding carboxylic acid. Synthesis via substituted benzhydryl chloride intermediates
Wang et al. had reported a successful coupling reaction of N-Boc- I decided to employ the following reaction strategy to introduce
L-leucine with tyramine [23], and since tyramine is structurally benzylpiperazine substitutions. First, I treated a previously synthe-
similar to benzylpiperazine, I decided to use the protocol outlined by sized Cbz-protected compound with 1-adamantyl acid chloride to
Wang et al. for the coupling of N-Boc-protected amino acids. Thus, produce the Cbz protected adamantylacetamide intermediate Int1:
N-Boc-glycine was coupled with commercially available 1-benzyl-
piperazine and 1-(3-tolyl)piperazine, with the two products then
deprotected by trifluoroacetic acid (TFA) and treated with the two
previously synthesized acid chlorides to yield Compound 3.0 as
well as three other analogs. Four products were formed (3.0 and
M1-M3, Table 1).3 Scheme 2. Formation of the adamantylacetamide intermediate Int1
Amino acid linker Int1 does not have a methylene linker adjacent to the adamantyl
In order to prepare derivatives of Compound 3.0 which differed group. This is important, since Compound 3.3 does not have the
only in the amino acid linker, different Boc-protected amino acids methylene linker and I am aiming to prepare derivatives of Com-
were used as starting materials. Instead of N-Boc-Glycine, ten other pound 3.3. A major problem with this synthetic route, however,
Boc-protected amino acids were treated with 1-benzylpiperazine in was in the purification step of Int1. Column chromatography and
analogous reactions. Products AA1-AA10 were formed (Table 2). SCX purification could not satisfactorily isolate the product from
the impurities, so mass-directed high-performance liquid chro-
Benzylpiperazine matography (HPLC) was performed. Even though this procedure
In the syntheses described above, 1-benzylpiperazine was used only returned 15.4% yield, the synthesis was ultimately success-
as one of the starting materials. In order to efficiently prepare ful, as confirmed when the purified Int1 was analyzed by NMR.
Removal of the Cbz protecting group with H2 and Pd/C yielded the
3. Structures and yields of all products synthesized in this study can be found adamantanecarboxamide-piperazine intermediate Int2. The reac-
in tables in the Discussion section. tion of Int2 with synthesized benzhydryl chloride intermediates to
www.thurj.org 95
Figure 4. Titration of viral activity using EBOV-GFP. The viral concentra- Figure 5. Test of GFP assay. (5a) 20 μM of Compound 3.0 and 4000 iu/mL
tion is 4100 iu/mL in 4a, 420 iu/mL in 4b, and 40 iu/mL in 4c. of EBOV-GFP. (5b) 20 μM of Compound 3.0, no virus. (5c) 4000 iu/mL of
EBOV-GFP, no compound. (5d) No compound or virus.
form the substituted benzylpiperazine 3.3 derivatives was unsuc-

cessful due to low yield, so another route was sought. ID MW Structure % Inhibition of
EBOV Infec-
Synthesis via Katritzky Reaction tion @ 5 μM
Another candidate approach modeled after a reaction in the
literature was then employed to synthesize the substituted benzyl- 3.0 409.6 90 ± 11
piperazine derivatives of Compound 3.3. Katritzky et al. had used
the benzotriazole group in an efficient electrophilic introduction
of an alkyl or aryl group onto a masked aldehyde with 50% to 94%
yield [24]. M1 395.5 28 ± 3
Chemical and
Based on Katritzky et al.’s work, I proposed the following reaction

Physical Bio
scheme to synthesize the substituted benzylpiperazine Compound

3.3 derivatives. The reaction scheme consisted of two steps. The
first step was to combine the three starting materials, including M2 423.6 90 ± 6
Int2, benzotriazole, and the substituted benzaldehydes in place of
Katritzy et al.’s masked aldehydes, in a centrifugal evaporator for
two hours to generate benzotriazole intermediates. Next, this ben-
zotriazole intermediate was reacted with the appropriate Grignard M3 409.6 61 ± 5
reagent to afford the desired final products.
Table 1. Synthesized 3.0 derivatives with variations in methylene linker
Anti-Ebola activity of Compound 3.0 derivatives
Experimental protocol
Several experiments needed to be completed before I could accu-
Scheme 3. Using Katritzky Reaction to synthesize Compound 3.3 derivatives rately test the derivatives. I chose to use the lab’s stock of EBOV-GFP
and Vero cells, which are a commonly used host cell for growing
A small scale reaction using benzaldehyde and methyl magne- virus. In order to determine the infectivity of the lab’s EBOV-GFP
sium bromide was run with the product successfully produced. on Vero cells, I ran a viral titering experiment.
After optimizing the conditions for the reaction and repeated the
reaction using a variety of benzaldehydes and Grignard reagents, Titration of viral infectivity
the twenty compounds 3.301-3.320 were successfully synthesized The infective titer was determined on Vero cells. I performed the
titration by diluting the stock of EBOV-GFP into 10-fold dilutions
Specific aim 2: Biological testing of 3.0 and 3.3 derivatives: and infecting the virus onto Vero cell monolayers in 96-well plates,
Dissecting antiviral activities. with each well containing 1.0 x 104 cells. The virus-cell mixture was
incubated at 37ºC for twenty-four hours, after which the number of
Rationale infectious foci labeled with GFP was counted under a fluorescent
Representative derivatives of the adamantyl group, methylene microscope. Two closely attached fluorescent cells were considered
linker, amino acid linker, and benzylpiperazine group of Compound as divided cells and counted as a single infected cell. From my titer-
3.0 were synthesized, along with derivatives of the benzylpiperazine ing experiment, 50 μL of the 1 mL 1:100,000 EBOV-GFP dilution
group of Compound 3.3. To assess the antiviral role of each part of resulted in an average of 420 infectious units (iu). Consequently,
the molecules, I tested these derivatives in an in vitro assay using the stock solution of EBOV-GFP was calculated to be 8.4 x 108 iu/
the green fluorescent protein (GFP) reporter gene. mL (Figure 4). 50 μL of the 1:10,000 EBOV-GPF dilution resulted in
around 4100 iu/well while 50 μL of the 1:1,000,000 EBOV-GPF dilu-
tion resulted in 40 iu/well, suggesting that there is a viral multiplicity
Compound 3.0 on EBOV and LV. From the data, Compound 3.0
had an IC50 value of 0.8 μM and an IC90 value of 5 μM.
GFP virus assay

To test my Compound 3.0 derivatives, I utilized a viral GFP assay
ID MW Structure % Inhibition of EBOV with which I could visually observe the results of viral infection in
Infection @ 5 μM compound-treated cells. A Vero cell monolayer was placed onto a
96-well plate, with 1.0 x 104 cells/well. For ten wells, I applied 20 μM
of Compound 3.0, let the virus-cell mixture incubate at 37ºC for
3.0 409.6 90 ± 6 three hours, and then added EBOV-GFP, 4000 iu/mL (Figure 5a).
For another ten wells I applied 20 μM of Compound 3.0 but did not
add the EBOV-GFP virus (Figure 5b). In ten other wells, I did not
add any Compound 3.0 but added the EBOV-GFP at 4000 iu/mL
AA1 423.6 IA (Figure 5c). Lastly, for ten more wells, I did not apply any compound
or virus (Figure 5d). From observing cell fluorescence indicative
of EBOV-GFP, I was able to confirm that EBOV membrane fusion
AA2 423.6 20 ± 4 led to GFP being produced, neither Compound 3.0 nor the Vero
cells themselves had any intrinsic fluorescence, and the number of
fluorescent cells was reduced by addition of compound inhibitors.
This assay served as a quantitative method to measure the relative
AA3 465.7 5±5 inhibitory strengths of my derivatives.
Chemical and
Physical Bio
Analysis of 3.0 derivatives
The GFP assay results on Compound 3.0’s derivatives are
AA4 451.6 IA discussed in Tables 1-5 below. Derivatives are listed with their
molecular weight (MW), chemical structure, and percent inhibi-
tion of EBOV-GFP. The inhibition values presented are the result
of the experiment being performed in triplicate and are relative to
AA5 571.8 78 ± 13 the fluorescence observed by dimethyl sulfoxide (DMSO)-treated
Vero cells, which was set at 100%. Functional groups of interest and
emerging trends are discussed following the results tables.
AA6 543.7 55 ± 6 Methylene linker

To evaluate the functional significance of the methylene linker,
I synthesized M1-M3 (Table 1) and tested their biological function
AA7 453.6 20 ± 5 with the aforementioned GFP assay in triplicate.
Amino acid linker

From Table 1, it was concluded that the methylene linker was
AA8 453.6 15 ± 4 important in conferring EBOV resistance, so it was retained in
future synthesis of Compound 3.0 derivatives. Derivatives AA1-
AA10 were synthesized to evaluate the functional significance of
the amino acid linker (Table 2).
AA9 448.6 28 ± 7 Benzylpiperazine

Derivatives B1-B31 were synthesized to evaluate the effects of
benzyl substitution on Compound 3.0’s benzylpiperazine group.
Table 3 is organized with electron-donating substitutions on the
AA10 449.6 35 ± 8 left column and electron-withdrawing substitutions and electron-
deficient rings on the right column.
Methyl substitution
Because of the strong anti-EBOV activity of M2 (Table 1), com-
Table 2. Synthesized 3.0 derivatives with variations in amino acid pounds B32-B37 were synthesized to further test the function of a
meta-methyl substitution on the benzyl ring.
of infection (MOI) of 1.
Adamantyl group
Dose-response curve of Compound 3.0 To test for the necessity of the adamantyl group in preventing
Another member of the lab produced a dose-response curve for EBOV infection, two 3.0 derivatives were synthesized (Table 5).
www.thurj.org 97
ubstitution on Compound 3.0’s benzylpiperazine group. Table 3 is organized with
RESEARCH
donating substitutions
AA5 571.8
O O
on the left column
78 ± 13 and
AA10 449.6electron-withdrawing
35 ± 8 substitutions and Volume 3 Issue 2 | Fall 2010
N
N
deficient rings on the right column.
H
2.2.2.5.3. Benzylpiperazine. Derivatives B1-B31 were synthesized to evaluate the effects of ID MW Structure % Inhibition
Synthesized 3.0 Derivatives with Variations in Benzylpiperazine
benzyl substitution on Compound 3.0’s benzylpiperazine group. Table 3 is organized with of EBOV
O N
electron-donating substitutions on the left column and electron-withdrawing substitutions and
Infection @
N 5 μM
N
electron-deficient rings on the right column.
H O
Table 3: Synthesized 3.0 Derivatives with Variations in Benzylpiperazine
% Inhibition O N % Inhibition
of EBOV N
Electron-withdrawing substitutions and of EBOV
MW Structure
Electron-donating substitutions
Infection,
N
H O ID MW
electron-deficient rings Structure Infection,
% Inhibition % Inhibition
5µM %ofInhibi-
EBOV of EBOV
% Inhibi-
5µM
ID MW Structure tion EBOV
ID MW Structure
ID MW Structure
Infection,
Electron-Withdrawing Substitutions and
ID MW Structure
Infection,
tion EBOV
ctron-Donating Substitutions 5µM
infection, 5µM
infection,
5µm
Electron-Donating Substitutions Electron-Deficient Rings
Electron-Withdrawing Substitutions
Electron-Deficient Rings
and
5µm
BrBr
3.0 409.6 95 ± 5 B16 488.5 85 ± 6
9.6 95 ± 5 B16 488.5 85 ± 6
O
Br
B1 439.6 94 ± 6 B17 488.5 87 ± 3
O
O
Br
9.6 B2 439.6 94 ± 686 ± 3 B17 488.5
B18 488.5 81 ± 4 87 ± 3
Br
Chemical and
OH
Physical Bio
B3 O
439.6 77 ± 4 B19 504.5 87 ± 11
9.6 86 ± 3
O
B18 488.5 Br
81 ± 4
O CN Br
B4 515.7 90 ± 5 B20 434.6 80 ±18
7
OH
O
CN
9.6 B5 515.7 77 ± 485 ± 7 B19 504.5
B21 434.6 92 ± 8 87 ± 11
O OH
B6 425.6 90 ± 8 B22 434.6 Br
67 ± 5 Table 4. Synthesized 3.0 derivatives with methyl substitution on benzylpipera-
CN CN zine group
O Cl
5.7 B7 425.6 90 ± 559 ± 3 B20 434.6
B23 478.5 75 ± 4 80 ± 7
OH
Cl
Cl ID MW Structure % Inhibition of
B8 423.6 90 ± 5 B24 478.5 83 ± 4
EBOV Infec-
Cl
N tion @ 5 μM
B9 423.6 83 ± 7 B25 410.6 27 ± 8
O
B10 466.6 50 ± 9 B26 410.6 N 29 ± 4
N
H
B11 453.6 79 ± 11 B27 410.6 25 ± 5

N
OH
F
F F
B12 459.6 82 ± 8 B28 477.6 87 ± 7
OH
F
F Table 5. Synthesized 3.0 derivatives with variations in adamantyl group
B13 475.6 95 ± 12 B29 477.6 F 83 ± 5
Cl Anti-Lassa activity of 3.3 derivatives

B14 459.6 83 ± 7 B30 444.0 91 ± 7
Experimental protocol
O
B15 453.6 90 ± 4 B31 444.0 86 ± 3 The central question concerning the Compound 3.3 derivatives
O Cl
is how Compound 3.3 inhibits LV infection. To test this, I used a
2.2.2.5.4. Methyl substitution. stock of LV-GFP on Vero cells in an experiment analogous to the
Table 3. Synthesized 3.0 derivatives with variations in benzylpiperazine one outlined in Figure 5.
Electron-withdrawing substitutions and

Determining IC90 of Compound 3.3
Electron-donating substitutions
electron-deficient rings
Compound 3.3 was tested for LV-GFP inhibition. I diluted Com-
% Inhibition % Inhibition
EBOV infection, EBOV infection, pound 3.3 into 10 μM, 20 μM, 25 μM, 30 μM, 35 μM, 40 μM, and
5µm 5µm
ID MW Structure ID MW Structure 50 μM and tested the various concentrations of the compound for
LV EBOV LV EBOV inhibition of LV-GFP entry into Vero cells. I found Compound 3.3
25μM 20μM 25μM 20μM
to have an IC50 value of 7 μM and an IC90 value of 17 μM.
GFP virus assay

Using the same assay as I did for EBOV-GFP, I tested twenty
derivatives of Compound 3.3 for anti-LV activity. I applied a Vero
cell monolayer onto a 96-well plate, with 1.0 x 104 cells/well. Since
the IC90 value of Compound 3.3 was 17 μM, to get inhibition even
closer to 100%, I used 25 µM of Compound 3.3 in as positive con-
trol. I applied 25 µM of each derivative compound onto the Vero
cell monolayer in triplicate, let the virus-cell mixture incubate at
37ºC for three hours, and then added in LV-GFP at 4000 iu/mL.
As negative control, I did not inject any compound inhibitors onto
three wells but still infected them with 4000 iu/mL of LV-GFP. The
100% infection rate is based off of the average of how many infec-
tious units fluoresced in the negative control wells.
Chemical and
Analysis of 3.3 derivatives
Physical Bio
Twenty derivatives of Compound 3.3 (Table 6, 3.301-3.320) were
successfully synthesized and tested for anti-LV and anti-EBOV
activity. I chose to test for anti-EBOV activity as well since Com-
pound 3.3 was originally a derivative of the anti-EBOV Compound
3.0, and so there was a chance that these Compound 3.3 derivatives
could inhibit EBOV as well as LV. Table 6 shows percent LV and
EBOV infection allowed, with 100% being the negative control
level with no inhibitor added to the cells. The percentages are an
average of two experiments, each done in triplicate, completed
under the same protocol.
One compound (3.302) seemed to confer both anti-EBOV and
anti-LV activity. This immediately suggests that substitutions on the
benzylpiperazine moiety of Compound 3.0 has significant effects
on the resulting compound’s specificity against different viruses.
Discussion
The main focus of this study was to try to understand how
Compound 3.0 and Compound 3.3 function in inhibiting EBOV
or LV membrane fusion. To do so, compound derivatives were
Table 6. Synthesized 3.3 derivatives with substitutions on benzylpiper-
systematically synthesized, confirmed for purity, and tested in
azine group. 20 μM of Compound 3.0 was used as positive control, and the
experiment was run in triplicate. biological assays for their potency in blocking viral infection. I
divided Compound 3.0 into four distinct groups: an adamantyl
group, a methylene linker, an amino acid linker, and a benzylpi-
Titration of viral infectivity perazine group.
The infective titer was determined on Vero cells. I performed
the titration by diluting the stock of LV-GFP into 10-fold dilutions Summary of results
and infecting the virus onto Vero cell monolayers in 96-well plates, None of the compound derivatives proved to be more effec-
with each well containing 1.0 x 104 cells. The virus-cell mixture was tive than the initial lead Compound 3.0 for anti-EBOV activity, or
incubated at 37ºC for twenty-four hours, after which the number of Compound 3.3 for anti-LV activity. A summary of my experimental
infectious foci labeled with GFP was counted under a fluorescent results is provided in Table 7.
microscope. The resulting viral infectivity was measured in infec- From this study, we have come to several conclusions about what
tious units per milliliter (iu/mL). From my titering experiment, 50 elements of Compound 3.0 and 3.3 are important in conferring
μL of the 1 mL of 1:10,000 LV-GFP dilution resulted in an average increased anti-EBOV and anti-LV activity. For optimum anti-EBOV
of 530 infectious units (iu). Consequently, the stock solution of activity, Compound 3.0 should not be changed. Thus, a compound
LV-GFP was found to be 1.1 x 108 iu/mL. must have present an adamantane group, a methylene linker, a
www.thurj.org 99
glycine amino acid linker, and an unsubstituted benzylpiperazine

Compound
Lead Virus Conclusions group. However, a meta substitution on the benzyl group if the
Sub-group
substituent is electron-donating, or an ortho substitution on the
3.0 Adamantyl EBOV Loss of adamantyl group corresponds to benzyl group if the substituent is electron-withdrawing, retains most
Group significant reduction in anti-EBOV activity of the parent compound’s anti-EBOV activity. Similarly, an ortho
(Table 5). substitution on a phenyl which is itself attached to the benzylpipera-
3.0 Methylene EBOV Removal of the methylene linker from Com- zine will retain must of Compound 3.0’s anti-EBOV activity. For
Linker pound 3.0 results in clear loss in anti-EBOV optimum anti-LV activity, Compound 3.3 should not be changed.
activity (Table 1) However, meta-substituted electron donating groups placed on the
3.0 Amino Acid EBOV Glycine confers the most activity. Long phenyl ring attached to the benzylpiperazine allows the compound
Linker aromatic substitutions on the amino acid to retain most of its anti-LV activity.
backbone fare better than small aliphatic The structure-activity relationship study not only helps in opti-
groups, which destroy antiviral function. mizing the structure of the inhibitor compound, but it can also
(Table 2). shed light on what intracellular processes are involved in the viral
3.0 Benzyl-piper- EBOV 1. Addition of a methyl at the meta position entry mechanism. Even though I have not conclusively identified a
azine on the benzene does not change 3.0’s antiviral cellular target that these compounds inhibit, I can claim that these
activity (Table 1) or even confers additional targets must be extremely specific and are key for both EBOV and
resistance (Table 4). LV infection, since I found that any changes in the structures of
2. For electron-donating substitutions, ortho either Compound 3.0 or Compound 3.3 will lead to a decrease in
substitutions on the benzyl ring confer the antiviral activity, no matter how small the change.
most anti-EBOV activity, followed by meta,
Chemical and
Compounds could be blocking cell targets

Physical Bio
then para substitutions. Fused rings are not

detrimental to inhibitory activity. (Table 3) Compounds 3.0 and 3.3 could be binding to a host cell receptor to
3. For electron-withdrawing substitutions, competitively inhibit GP1 binding. This receptor could be a channel,
meta-substitutions on the benzyl ring con- since the adamantane group that we have concluded to be crucial
fer the most anti-EBOV activity, followed by for antiviral activity has already been identified as necessary for
ortho, then para substitutions. (Table 3) inhibiting a key viral M2 proton channel [13] activated at low pH
3.3 Benzyl-piper- LV 1. Meta-substituted electron-donating groups in influenza A infection. The target could also be a surface receptor
azine conferred the most anti-LV activity. (Table 6) for EBOV GP. If this is the case, Compounds 3.0 and/or 3.3 might
2. Putative receptor for LV infection is specific block this putative receptor, preventing the virus from entering
for the size of the aliphatic group replacing the endocytic pathway necessary for viral membrane fusion. If the
phenyl in Compound 3.3 (Table 6) compounds indeed bind to a specific receptor, they must be very
3. Both electron-donating and electron- potent, since it is difficult for a small molecule-receptor interaction
withdrawing substitutions on the phenyl ring to disrupt a ligand-receptor interaction due to the much lower bind-
follow a trend of decreasing anti-LV activ- ing energy. The structural similarity of compounds 3.0 and 3.3, as
ity with meta, para, and ortho substitutions, well as the existence of at least one derivative (3.302) which seems
respectively. (Table 6) to have both anti-EBOV and anti-LV activity, suggests that EBOV
4. The more electronegative the halogen and LV might even have receptors that are closely related.
substitution is on the phenyl ring, the more
anti-LV activity the compound has. (Table 6) Compounds could be blocking transport of vesicles to
5. Bromine substitution switches viral speci- lysosome
ficity (Table 6). EBOV and LV are first taken into the cell into endosomes. These
6. Breaking the aromaticity of the phenyl ring endosomes can either mature to become late endosomes and lyso-
makes the compound lose antiviral activity. somes as their internal pH drops via proton pumps, or they can
(Table 6) fuse directly with lysosomes. In order for successful fusion, the
3.3 Benzyl-piper- EBOV 1. Both electron-donating and electron- lysosomes must be recognized by the endosome via a signaling
azine withdrawing substitutions on the phenyl ring pathway. Compounds 3.0 and 3.3 could be blocking this signaling
follow a trend of decreasing anti-EBOV activ- pathway to prevent the successful trafficking of late endosomes to
ity with ortho, meta, and para substitutions, lysosomes. If the virus cannot get into the lysosome where cathep-
respectively. (Table 6) sins are located, membrane fusion will be inhibited, since it was
2. The more electronegative the halogen shown that cathepsin activity is required for membrane fusion [9].
substitution is on the phenyl ring, the less
anti-EBOV activity the compound possesses. Compounds could be affecting intralysosomal activity
(Table 6) Lysosomes are filled with many important enzymes and prote-
3. Breaking the aromaticity of the phenyl ring ases, including the cathepsins CatL and CatB, both of which have
makes the compound lose antiviral activity. been shown to be crucial for EBOV membrane fusion. Compounds
(Table 6) 3.0 and 3.3 could even be inhibiting some of these intralysosomal
enzymes to prevent successful viral entry.
Table 7. Summary of experimental results: 3.0 and 3.3 analogs

Conclusion 3.0 (Figure 6). Compound 3.47 incorporates many conclusions I

made for optimizing anti-EBOV activity. It possesses an adaman-
This work builds upon the identification of the new anti-EBOV tyl group, a methylene linker, a glycine amino acid, and an ortho,
adamantane-carboxamide inhibitor, Compound 3.0, and anti-LV electron-donating substitution on the benzylpiperazine.
adamantylacetamide inhibitor, Compound 3.3. An effective syn- Since Compound 3.47 inhibits in the nanomolar range, it is
thetic route of adamantanecarboxamide and adamantylacetamide by far the best derivative of Compound 3.0 so far synthesized. It
derivatives was achieved in Specific Aim 1 to create an SAR library also has the additional advantage that it possesses an ester group
of each parent compound. That SAR library was then tested for to which linkers can be fused to serve as cellular markers. Recent
antiviral activity in Specific Aim 2 and conclusions were drawn as work in the lab has led to the attachment of long linker with either
to how each family of compound functions. a BODIPY fluorophore or a benzylphenone group attached at the
end without inhibiting antiviral activity. The BODIPY fluorophore
Target identification can light up any compartment that it is in, so by using 3.47-BODIPY,
An immediate goal is to use these adamantanecarboxamide and the exact location of the inhibiting compound can be discerned.
adamantyl-acetamide inhibitors as probes to identify cell factors Benzylphenone, on the other hand, forms a covalent bond with
that mediate virus infection. The approach will be to modify the whatever is nearby when activated with UV light. If the addition
inhibitors with chemical tags which facilitate binding and recovery of a reactive azide disrupts the anti-viral activity of 3.47, an alter-
of target proteins. A click chemistry scheme is being devised using native strategy will be to radiolabel and biochemically purify the
the conclusions in the present study. Benzyl regions of the com- cross-linked target. Yet another possible method to identify host
pound derivatives are linked with an acyl chain containing terminal factors using benzylphenone is to use click chemistry. Overall, 3.47
reactive benzylphenone and azide moieties, which will form covalent represents a significant step to the identification of a host cell target
bonds with adjacent proteins in UV radiation, including the key via adamantanecarboxamide inhibitor.
Chemical and
host factors. After this crosslinking, cell lysates will be treated with
Physical Bio
biotin-base reagents which form specific covalent bonds with the Drug potential
azide moieties on the inhibitor compound. The crosslinked target Target identification allows for the specific, tailored develop-
proteins, receptors, or other host targets are pulled out of the lysate ment of more effective drugs, since it allows for the understanding
on streptavidin beads during affinity chromatography. Since these of the pertinent biological pathways. The present study represents
covalent bonds are irreversible, purification of the target can proceed part of an ongoing process towards target identification of a small
without the concern for loss of compound-target interaction. After molecule EBOV or LV inhibitor. Identification of such a host target
recovery, these proteins can be identified by mass spectroscopy and would contribute greatly to molecular as well as clinical progress in
tested directly for their role in infection. creating the first anti-EBOV drug, as an anti-LV drug, Ribavirin,
has already been produced.
Initial progress in development of tagged inhibitors: Ebola hemorrhagic fever causes fatalities ranging from 50% to
Compound 3.47 90% and treatment is currently limited to basic supportive care
The analysis of adamantanecarboxamide and adamantylacet- [14]. Currently there is no vaccine, so the development of an anti-
amide compounds outlined in this study have indicated that the EBOV drug would be a landmark step. Even though none of the
benzyl ring of this particular family of inhibitors was a potential Compound 3.0 and 3.3 derivatives in the present study are active
site to accept chemical tags without compromising antiviral activ- in the optimal nanomolar or picomolar concentrations for drugs,
ity. Based on this and several other conclusions from this work, several interesting conclusions were reached, such as the forma-
including that electron-donating groups should be substituted in tion of the adamantanecarboxamide Compound 3.47, which might
the ortho position onto the benzyl ring on the end of the molecule, contribute to eventual drug formation.
Compound 3.47, which was recently synthesized in the lab, has at These conclusions are encouraging also because both Compound
least twenty times the anti-EBOV activity of the parent compound 3.0 and Compound 3.3 possess an adamantyl group, which is already
Figure 6. (6a) Structure of 3.47. (6b) Dose-response curve of 3.47 against EBOV and LV. 3.47 is shown to have an IC90 in the nanomolar concentration.
www.thurj.org 101
shown to have antiviral activity against influenza. Anti-influenza 3. White JM, Delos SE, Brecher M, Schornberg K. Structures and mechanisms
A adamantane drugs inhibit the M2 proton channel, a tetrameric of viral membrane fusion proteins: multiple variations on a common theme.
protein which equalizes the pH between the virus and the endo- Crit. Rev. Biochem. Mol. Biol. 2008;43(3):189-219.
some of the host cell. This finding raises the possibility that the 4. Bär S, Takada A, Kawaoka Y, Alizon M. Detection of cell-cell fusion medi-
host factor to which the compounds bind might have a similar ated by Ebola virus glycoproteins. J. Virol. 2006;80(6):2815-2822.
conserved structure from this channel. At the same time, these 5. Volchkov VE, Feldmann H, Volchkova VA, Klenk HD. Processing of the
adamantanecarboxamide and adamantylacetamide compounds Ebola virus glycoprotein by the proprotein convertase furin. Proc. Natl.
are not structurally similar to any proposed anti-EBOV or anti-LV Acad. Sci. U.S.A. 1998;95(10):5762-5767.
drugs, which may suggest that they inhibit a different part of the 6. Kaletsky RL, Simmons G, Bates P. Proteolysis of the Ebola virus glycoproteins
sequence of steps leading to membrane fusion. For example, the enhances virus binding and infectivity. J. Virol. 2007;81(24):13378-13384.
known anti-LV Ribavirin is not particularly similar to Compound 7. Weissenhorn W, Carfí A, Lee KH, Skehel JJ, Wiley DC. Crystal structure
3.0, Compound 3.3, or any of their derivatives from this study. of the Ebola virus membrane fusion subunit, GP2, from the envelope gly-
The development of an anti- EBOV drug might have other impor- coprotein ectodomain. Mol. Cell. 1998;2(5):605-616.
tant consequences, as well. EBOV is perhaps the best known and 8. Kuhn JH, Radoshitzky SR, Guth AC, et al. Conserved receptor-binding
most well-studied example in a taxonomically diverse group of domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a com-
viruses which cause viral hemorrhagic fever. Conclusions reached mon receptor. J. Biol. Chem. 2006;281(23):15951-15958.
from EBOV mechanism investigation has influenced how we view 9. Chandran K, Sullivan NJ, Felbor U, Whelan SP, Cunningham JM. Endo-
other viruses which cause hemorrhagic fever, including Marburg, somal Proteolysis of the Ebola Virus Glycoprotein Is Necessary for Infection.
Lassa, South American arenaviruses, yellow fever, and Rift Valley Science. 2005;308(5728):1643-1645.
fever viruses. These viruses may share commonalities in their entry 10. Aman MJ, Bosio CM, Panchal RG, et al. Molecular mechanisms of filovirus
mechanisms, and so any progress on understanding the EBOV cellular trafficking. Microbes Infect. 2003;5(7):639-649.
Chemical and
mechanism might help to elucidate analogous processes.

Physical Bio
11. Wool-Lewis RJ, Bates P. Characterization of Ebola virus entry by using

pseudotyped viruses: identification of receptor-deficient cell lines. J. Virol.
1998;72(4):3155-3160.
References 12. Schornberg KL, Shoemaker CJ, Dube D, et al. Alpha5beta1-integrin controls
ebolavirus entry by regulating endosomal cathepsins. Proc. Natl. Acad. Sci.
1. Harrison SC. Viral membrane fusion. Nat. Struct. Mol. Biol. U.S.A. 2009;106(19):8003-8008.
2008;15(7):690-698. 13. Schnell JR, Chou JJ. Structure and mechanism of the M2 proton channel
2. Zampieri CA, Sullivan NJ, Nabel GJ. Immunopathology of highly of influenza A virus. Nature. 2008;451(7178):591-595.
virulent pathogens: insights from Ebola virus. Nature Immunology. 14. Geisbert TW, Jahrling PB. Exotic emerging viral diseases: progress and
2007;8(11):1159-1164. challenges. Nat. Med. 2004;10(12 Suppl):S110-121.

The role of the informal sector in equitable

water distribution: A case study of the
tanker market in Ayn al-Basha, Jordan
Sarah Hinkfuss, ‘10
Harvard University, Department of Economics
This paper investigates the extent to which the informal water market equitably distributes water to urban
households. Stated differently, given a government monopoly that falls short of its purpose, can the “invisible
hand” equitably distribute a precious resource? Development economists commonly find evidence of ethnic dis-
crimination—here defined as horizontal inequity—and regressive pricing—here defined as vertical inequity—in
free market settings, while contradictory neoclassical analysis suggests that mutual self-interest will result in a
naturally equitable marketplace. The paper probes this under-researched question by constructing a household
water demand model with household-level data gathered during a field survey in July and August 2009 of 265
households in the Emir Ali neighborhood of Ayn al-Basha, Jordan. The paper uses the household water demand
model to analyze the equity characteristics of the local water market using OLS and IV methods. The results
suggest that the informal market is non-discriminatory but exhibits regressive pricing, which implies that the
informal market falls short of a truly equitable distribution.
Introduction Ayn al-Basha, Jordan as a case study, I find mixed results: the infor-
mal market is non-discriminatory, but exhibits regressive pricing.
“You have to assure equality for the neighborhood to accept In brief, the findings presented in this paper are based on empiri-
stress. Then the challenge of water storage, call it, creates a cal, qualitative, and quantitative case study research. The basis of
unity of purpose.” the study is a randomized survey of households I conducted in Ayn
Economics
-Former Jordanian Minister of Water and Irrigation al-Basha during August 2009. The survey concerned household
10 August 2009 demographics, water use, and water satisfaction. I also conducted in-
depth interviews of key informants at the local and national levels,
In an interview, Munther Haddadin, the former Jordanian Min- including those in the health care sector, the local water authority,
ister of Water and Irrigation, summarized the implications of his the national water office, and private water firms. Despite detailed
country’s water scarcity on the optimal distribution of the resource study of the local context of water service provision, the case study
at the household level: “Local water stress can only be met with of Ayn al-Basha is necessarily a snapshot in time. My work remains,
a unity of purpose, which requires equity” (Interview K, 2009). however, the first step into an under-researched field.
Local distribution of water in Jordan occurs through not only the This paper presents the first econometric foray into understand-
formal sector—the public water utility—but also through informal ing how the informal market distributes water to urban households.
entrepreneurs who sell water from tanker trucks to households. As climate change accelerates the aridity of already water scarce
Equity in the formal market is ensured by 91% access rates and a countries—namely those in the Middle East—establishing mecha-
progressive tariff structure (World Development Indicators, 2005). nisms that equitably distribute this precious resource will become
In the tanker market, however, the level of equity is unknown. matters of domestic political stability and global security. Higher
There are two types of equity: horizontal equity and vertical water scarcity will likely mobilize the informal market to play a
equity. Horizontal equity concerns the similar treatment of all greater role in resource distribution. Development economists and
similar households and the dissimilar treatment of all dissimilar natural resource practitioners must understand the informal market
households. The designation of a similar versus a dissimilar house- and find ways to improve its performance. The inter-disciplinary
hold should only be made on the basis of willingness to pay (WTP) methods mobilized in this paper can be applied to other informal
differences among households and not on issues of race, ethnic- markets in the region.
ity, or religion. I call horizontal inequity discrimination. Vertical
equity occurs when pricing is progressive, like progressive taxation The household water market and the invisible hand
(Mohamed, Kremer, and Kumar, 2009). The formal sector in Jordan inadequately distributes water due
This paper investigates the extent to which the informal water to the country’s severe water scarcity (FAO, 2009). In response
market improves the horizontal and vertical equity of water access to its extremely low levels of water, the Jordanian government
and distribution. Stated differently, given a government monopoly rations water and residents store it in tanks. Local entrepreneurs
that falls short of its purpose, can the “invisible hand” equitably capture residual household water demand by selling spring water
distribute a precious resource? Using the Emir Ali neighborhood of directly to households from water tanker trucks. The water tanker
www.thurj.org 103
market exhibits the three characteristics of the market laid out in surveying to determine household preferences and WTP for
by Adam Smith: the interaction of supply and demand, compe- water services in rural South Africa. The households surveyed had
tition, and self-interest (Smith, 1759). The tanker market is the inconsistent water access. The authors find that households with
informal market—not just a private market—because the tanker lower incomes have higher price elasticity, which negatively impacts
drivers’ operation depends on the Water Authority Jordan (WAJ) their WTP, as compared to more well off households. Strand and
not regulating the tanker prices. The tanker market operates with- Walker (2005) find income elasticities below 0.1.
out meaningful institutional oversight or regulation (Interview N, While there is some disagreement on the particular level of
2009; Odeh, 2009; Sass and Brubach, 2008). income elasticity, there is near universal agreement that household
Household demand in the informal water market, let alone the demand for a primary source of water exhibits positive income
level of equity in the market, is currently poorly understood. Two elasticity. Hajisyprou, Koundouri, and Pashardes (2002) establish
competing hypotheses exist on the ability of this special water the theoretical basis of water as a normal good, and Le Blanc (2008)
market to equitably distribute the resource. On the one hand, empirically demonstrates this finding. He finds that household
neoclassical economic analysis suggests that the tanker market expenditures on water increase with income, but less than linearly.
results in equity gains because it exists as a free market response In South Asia, Le Blanc finds that households spend, on average,
to the inefficiencies of the public market. Both the suppliers and 2% of their income on water consumption. The share of income
consumers voluntarily enter the market so even if there is inequity, it increases to 3.5% in Latin America and Eastern Europe. No com-
must improve welfare based on the assumption that households are parable review papers consider the Middle East.
rational economic actors. On the other hand, development economic The preponderance of the literature on household demand for
analysis suggests that households have no choice but to enter the water from the informal market is based on studies in peri-urban
informal market to meet household water needs. As a result, these areas where the informal market is the sole supplier of water to
households exhibit extremely inelastic demand for water and must these households. In such situations, the household water demand
accept the price set by the suppliers. The tankers maximize profit exhibits the same qualities as the demand for water from the formal
by favorably distributing to households in their family network, sector. This is not representative of Ayn al-Basha, however, because
which creates inequity in the forms of discriminatory distribution households use both the piped water and tanker water supply. When
and a regressive pricing scheme. households are presented with water from the informal sector to
supplement or substitute water from the formal sector, such as in
Local context my study area, then demand may be different. In fact, Strand and
Ayn al-Basha is a city in the Balqa governorate, adjacent to Walker (2005) note an enormous effect of the water’s source on
Amman, the capital city of Jordan. Emir Ali is a small neighbor- the household’s level of demand elasticity. Additionally, numer-
hood of about two square kilometers and 1,383 households (Dorsch ous papers by Dale Whittington find that the mix of water supply
Consult, 2007). This area is ideal to study the informal water market sources available to households changes the optimal household
Economics
for four reasons: consumption of the various sources (Whittington and Bal Kumar,
1. Emir Ali, with its exclusive Muslim majority and level of 2005).
water scarcity, is representative of other areas in the region (Depart- Only one paper constructs household demand in the informal
ment of Statistics, Jordan, 2006; Sass and Brubach, 2008). Hence, this market based on observed behavior. Many other authors, such as
case study may be meaningfully generalized to the greater region. Whittington, use the household cost of coping mechanisms and
2. The local tanker water market is robust because household contingent valuation surveys to estimate household water demand
water demand is greater than piped water supply due to the use of (Whittington, et al., 1990; Whittington and Bal Kumar, 2005; Whit-
sub-par materials and low-skilled public workers. tington, Lauria and Mu, 1991; and Whittington, Mu, and Roche,
3. Both public workers and households in the area are familiar 1990). Iskandarani’s (2001) seminal paper is notable not just because
with foreign water professionals who work in coordination with it applies econometric analysis to a new market, but also because
international organizations. she does so in Jordan.
4. The neighborhood exhibits high levels of ethnic diversity Iskandarani (2001) models household demand for the tanker
because it is adjacent to the Baqa’a Palestinian refugee camp. This market based on a household survey of 200 households in Jordan
enables the exploration of discrimination issues. conducted in the summer of 1999. She first models the discrete
choice of households to consume tanker water based on the price
Literature review of the tanker water, the amount of piped water that the household
The empirical literature confirms that household water demand receives, their monthly income, their water storage capacity, and
obeys the law of demand. First, water demand increases as house- their level of satisfaction with piped water supply. Iskandarani
hold size increases, but less than proportionally due to household does not explain, however, why households have a choice at all over
economies of scale (Strand and Walker, 2005; Whittington and Bal what type of water to consume and if the quantity of piped water
Kumar, 2005). Second, numerous studies establish that household is set exogenously. Iskandarani finds that household demand for
demand for primary sources of water is inelastic, which is consistent tanker water is price inelastic and that when the full price of water
with demand for a necessary good (Ruijs, Zimmerman and Van is considered, households spend more than 3% of income on water
den Berg, 2008; Strand and Walker, 2005). than is currently assumed.
In addition to demand elasticity, many authors consider income
elasticity. Kanyoka, Farolfi, and Mordet (2008) analyze demand and !"#$"%#&'()'*+#',-,#$
income elasticity by considering how demand elasticity of a house- The paper proceeds in four sections. Section II presents the
hold changes as income changes. Their model uses a choice approach theoretical model of household water demand. The assumptions
Figure 2a Figure 2b
of the model are based on the dominant assumptions in the lit- quantities of household water consumption the household already
erature and my assessments from fieldwork. The model predicts has sufficient water and needs a large decrease in the price to war-
both horizontal and vertical inequity. Section III describes the data rant purchasing any additional quantities. The household demand
mobilized to evaluate the theoretical model. Section IV uses the curve for tanker water that exhibits these characteristics is shown
data to empirically investigate the informal water supply in Emir in Figure 2a.
Ali neighborhood. I construct household demand for tanker water The supply relationship is similarly constructed. Tanker driv-
using instrumental variables, as suggested in the water demand ers exhibit a degree of power in setting prices, which allows them
literature. I find no evidence of horizontal inequity and some evi- to better recover costs and increase profits. In essence, this means
dence of vertical inequity. Finally, Section V concludes. the more a given household consumes, the higher price the tanker
As demonstrated in the literature review, very few microeco- driver will charge the household for the water. The tanker supply
nomics papers convincingly construct household demand for water curve exhibits monopolistic competition.
from observed household behavior, let alone demand for a good in The interaction of the demand and supply curves creates the
the informal market. This paper advances the natural resource and tanker water market, as in Figure 2b. The optimal allocation of
development economics literature by addressing this challenge. water, MM, occurs at the intersection of the curves.
One would expect all households of similar income levels to share
Economics
the same equilibrium point. However, my interviewees suggested
Theoretical model that at each income level, Jordanians, or those with influential family
networks, are preferentially served by the market relative to Pales-
“If you don’t have (money), then consume less…and some tinians, or those without influential family networks. Jordanians
people, they wash the trees.” are native to the country, and Palestinians are considered immi-
-Answer of a water official in response to a question about grants, even if a Palestinian was born in Jordan. Jordanian families
varying water use among local households, 11 August 2009 dominate government positions and are considered more powerful
through their ties to the King. Although both ethnic groups may
This chapter presents an analytical framework for determining access the market, ethnicity results in two market demand curves
the equity of the private water market operating in tandem with and water allocations rather than one, as shown in Figure 2c. If true,
the public market. The framework models and evaluates horizontal this violates horizontal equity. This conclusion is expected because
and vertical equity in the tanker market. To do this, I first con- tanker water is distributed within family networks, so tanker driv-
struct a theoretical model of household water demand. From there, ers set lower prices to their family than to other consumers. Given
I examine both whether the household characteristics that influence that families are all of one ethnicity, the model predicts the tanker
water demand are congruent with horizontal equity and whether market is horizontally inequitable because the price the tanker
the dominant pricing structure exhibited by the demand curve is driver sets for water is determined by ethnicity.
consistent with vertical equity. Additionally, the shape of the demand curve presented predicts
I build household demand for tanker water based on fundamen- that the tanker market will be vertically inequitable. As in Figure
tal water needs. Households require a certain quantity of tanker 2d, the quantity of water consumed by poor households is closer
water for basic survival and will pay all of their income, short of to their minimum survival level, where demand is near completely
income for other necessary goods like food and shelter, to receive inelastic. Therefore, price-setting tanker drivers may improve their
this quantity. Household consumption at all quantities less than or profit margin by exploiting this high inelasticity and setting higher
equal to the survival quantity will take place irrespective of the price prices for poor consumers than for wealthy ones.
of the tanker water. Once the basic quantity is secured, however, The appendix derives a model of household water demand for
household willingness to pay (WTP) for water is a function of its to support these predictions.
price, and households will consume less water as the price increases.
At low quantities of household water consumption, a small decrease Theoretical applications of the model on equity
in price induces a large increase in water consumed, while at high The theoretical model of the tanker market forms the basis for
www.thurj.org 105
Figure 2c Figure 2d
predicting the extent to which the tanker market improves equity households. The difference in demand between the ethnicities peaks
in the water market. An analysis of horizontal and vertical equity at a consumption quantity past the minimum level of water required
in the water market surveys the household distribution of access to by the household. Additionally, as the Jordanian demand curve is
fairly priced, high-quality, reliable, satisfactory water. The model always greater than the Palestinian demand curve, the Palestinian
captures household access by the quantity received and the price households have less elastic demand, as the model predicts.
paid at the household’s optimal demand. The demand defines the
household’s willingness to pay for the water, or the value of the Vertical equity
tanker water to the water. The theoretical model predicts that the tanker market is verti-
cally inequitable. As explored in the horizontal equity section, the
Horizontal equity theoretical market model predicts that Palestinian households will
Evidenced by the role of C in the theoretical model, the tanker pay more per cubic meter because the tanker drivers will respond to
market is horizontally inequitable because household ethnicity the differential WTP by charging the Palestinian households more
mediates household access to tanker water. The discrimination effect to exploit the associated efficiency gains. The additional price that
is demonstrated in the optimal quantity demanded, the elasticity of the Palestinian households must pay to consume the same amount
demand, and the income elasticity. Holding all else constant, Equa- of water as their otherwise equal Jordanian counterparts is double
Economics
tion (15) in the Appendix predicts that Palestinian households will the price that the Jordanian households pay.
consume an amount less of tanker water than Jordanian households.
(18)
(16) The pricing structure is most regressive when the level of piped
Likewise, holding all else constant, Equation (16) predicts that water consumed by the household does not meet the household’s
Palestinian households will have less elastic demand than Jordanian Mmin for two reasons. First, poor households are more inelastic in the
households across all quantities. tanker market than in the piped water market, given the elasticity of
piped water supply. Second, usually a small increase in price means
that the tanker driver will lose a considerable amount of quantity
(17) supplied, however households have extremely high tolerance for
Equations (16) and (17) demonstrate that Palestinian households price increases in their survival surplus portion of the demand
derive less utility from a given quantity of tanker water consumed curve. Therefore, tanker drivers may face an incentive toincrease
than their Jordanian counterparts. Finally, holding all else constant, prices for households that consume less water, which in most cases
Equation (15) in the Appendix predicts that the income elasticity of are the poorest households.
Palestinian households will be half that of the Jordanian households.
Lower income elasticity means that Palestinian households across Limitations of model and theoretical analysis
different income groups will have less variation in tanker water The theoretical model is the best approximation for actual behav-
consumption patterns than Jordanian households and be charged ior in the tanker market in Ayn al-Basha because the assumptions
more at every quantity consumed than their identical Jordanian are based on observation and interviews and not solely on existing
counterparts. None of the other variables in the theoretical model models. However, no model can capture the diversity of choices
pose a threat to the horizontal equity criteria. facing households and their resulting behaviors. For example, the
Figure 2c illustrates the horizontal inequity of the model. The model does not account for family time investments in consuming
figure modifies the depiction of the household demand curve to tanker water, such as boiling and freezing water, and the quality
represent only the price, φ, along the y-axis, rather than φC as in the and reliability of tanker water may impact the vertical equity of
other figures. C impacts the shape of the household demand curve. the market based on which households disproportionately bear
The graph shows that for equivalent levels of consumption, Jorda- the costs of low quality and unreliable water. Additionally, wasta
nian households always pay less per cubic meter than Palestinian is not as simplistic as a binary variable that represents household
ethnicity. There are enormous ranges of influence demonstrated by household script were randomly distributed throughout the area
households. Future iterations of the model should relax the assump- and more often than not occurred on the first day of a translator’s
tion of wasta as a binary variable. time with me.
Variables for the empirical investigation

Data !"#$%&'()&*$+)&'),-#.$/.#0$'1$2"#$)1)-*.'.$)&#$2"#$0#%#10#12$
)10$'10#%#10#12$+)&'),-#.3$!"#$4#*$0#%#10#12$+)&'),-#$'.$2"#$2&'5
“Studies are needed to focus on understanding the nature of house- (612"-*$761./(%2'61$68$2)14#&$9)2#&3$:$761.'0#&$)--$"6/.#"6-0.$'1$
hold demand for water and should attempt to express it in terms 2"#$./&+#*$)&#);2"6.#$2")2$761./(#$2)14#&$9)2#&$)10$2"6.#$2")2$06$
of household demand functions.” -An appeal for new research by 162$761./(#$2)14#&$9)2#&3$!"#$2&'5(612"-*$761./(%2'61$'.$2"#$262)-$
Munther Haddadin, the Former Minister of Water and Irrigation +6-/(#$68$)$"6/.#"6-0<.$=&6/10$-#+#-$)10$&66826%$2)14#&.>$(/-2'%-'#0$
in his 2006 book, Water Resources in Jordan ,*$2"#$%&6,),'-'2*$2")2$2"#$2)14#&$9)2#&$76(#.$0)'-*>$(/-2'%-'#0$,*$
?@$86&$2"#$1/(,#&$68$0)*.$'1$2"&##$(612".3$:8$)$"6/.#"6-0$06#.$162$
The quality of the data available to a study determines the basic 761./(#$2)14#&$9)2#&$2"#1$2"#$8)('-*$").$)$A#&6$%&6,),'-'2*$68$7615
value of an empirical investigation. My data comes from three ./('1=$2)14#&$9)2#&$61$)$='+#1$0)*>$)10$2"#$"6/.#"6-0<.$2&'5(612"-*$
sources. First, the Water Authority Jordan (WAJ) central statistics 761./(%2'61$68$2)14#&$9)2#&$'.$@3$:$/.#$)$2"&##5(612"$2'(#$%#&'60$
office in Amman provided the household-level piped water data. ,#7)/.#$2"'.$'.$2"#$%#&'60$6+#&$9"'7"$%'%#0$9)2#&$,'--'1=$677/&.3
Second, I used Geographic Information Systems (GIS) to interpret The key independent variable is the per cubic meter cost of tanker
all of the household-level geographic relationships from the maps water. As in many other utility markets, no distinction can be made
of Emir Ali neighborhood in Ayn al-Basha. Engicon produced between the average and marginal cost of the tanker water due to
the maps in coordination with Dorsch Consult. Third, all other the structure of this question in the survey. The question asked
household-level data comes from a randomized household-level respondents: “How much do you pay per cubic meter for water
survey that I conducted in Ayn al-Basha during 2009. Each set from tankers?” The price included in the regressions, thereby, is the
of data offers its own advantages and limitations that in concert average price and the marginal price is indeterminate.
uniquely qualify this paper’s novel investigation of equity in the !"#$#(%'&'7)-$'1+#.2'=)2'61$68$#B/'2*$&#-'#.$61$2"#$)77/&)7*$)10$
informal market. %&#7'.'61$68$296$"6/.#"6-05-#+#-$7")&)72#&'.2'7.C$'176(#$)10$#2"5
1'7'2*3$D#=)&0'1=$"6/.#"6-0$#2"1'7'2*>$2"'.$9).$=)2"#&#0$7)&#8/--*$
Methodology )10$'17'0#12)--*3$E.$)$86&#'=1#&>$'2$9).$'1)%%&6%&')2#$)10$%6-'2'7)--*$
To collect the household level information, I conducted a ran- '176&&#72$'1$)--$7'&7/(.2)17#.$26$).4$)1*$'10'+'0/)-$"'.$6&$"#&$#2"5
domized household survey of 295 households (ME 1.8%) over three 1'7'2*3$F)1*$-67)-.$&#=)&0$2"'.$26$,#$)1$'(%&6%#&$B/#.2'61$26$).4$
weeks during July and August 2009, in the Prince Ali neighborhood #)7"$62"#&$).$9#-->$)-2"6/="$)2$2'(#.$(*$2&)1.-)26&.$#176/12#&#0$
Economics
of Ayn al-Basha. Pre-field work, I randomly chose the households &#.'.2)17#$9"#1$2"#$'12#&+'#9##$&#8/.#0$26$7612'1/#$/1-#..$2"#$
to be surveyed using a uniquely identifying houseplot number. 2&)1.-)26&$.)'0$26$,#$68$2"#$'12#&+'#9##<.$#2"1'7'2*3$G6/.#"6-0$#2"5
The surveys followed a script and were conducted in Arabic with a 1'7'2*$9).$&#76&0#0$61-*$9"#1$61#$68$2"#$86--69'1=$2"&##$.'2/)2'61.$
translator unless the respondent elected to speak in English. 677/&&#0C$2"#$'12#&+'#9##$+6-/12##&#0$"'.$6&$"#&$#2"1'7'2*$0/&'1=$
The final sample is only 265 households. Ten households declined 2"#$76/&.#$68$2"#$./&+#*H$2"#$'12#&+'#9##$=)+#$"'.$6&$"#&$./&1)(#$
to participate in the survey, I was unable to interview seven house- )10$2"#$./&1)(#$'.$41691$26$,#$68$61#$#2"1'7'2*$6&$)162"#&H$6&$2"#$
holds, and an additional thirteen surveys had to be excluded due to '12#&+'#9##$.%64#$'1$2"#$0')-#72$761.'.2#12$9'2"$61#$#2"1'7'2*$6&$
failure to follow the survey script. The respondents at households )162"#&3
who declined to participate did so only when I was with a male
translator. I speculate that this was due to the cultural apprehen-
sion about speaking with non-familial males. These families were Empirical investigation
scattered throughout the study area, so I expect their exclusion to
create no bias in the survey. At the seven households where I was “Water didn’t come this week and pressure was bad last week, so
unable to find someone to interview, the house itself was either we haven’t bathed....”
under construction or there were only family members under the -Household 252 describing her satisfaction with the quantity of
age of 18 at home. The exclusion of the households under construc- water supplied, 19 July 2009
tion has little bearing on the distribution of households included in
the survey because these houseplots do not yet represent families This chapter empirically tests the predictions of horizontal and
demanding tanker water until they live in their homes. vertical inequity in the tanker market from the model in Section
On the other hand, the second class of families who I was unable II with the data described in Section III. The objective of this sec-
to interview due to no adult being present are likely the very poor tion is three-fold: first, to confirm empirically the assumptions of
families in which both parents (and any grandparents) select to the theoretical model; second, to construct household demand
work outside of the home and do not come home for lunch time for tanker water; and third, to use demand to test the predictions
(as is customary). As I only surveyed during normal working hours of horizontal and vertical inequity from the theoretical analysis.
(8AM to 4PM), these very poor households are thus excluded. I begin by confirming two assumptions underlying the theoreti-
Consequently, my equity analysis will likely overestimate the true cal model: one, the tanker water is a uniform good, or a good that
equity effects because the poorest of the poor have been excluded. is identical across all units sold; and two, all households have equal
Finally, the households who were excluded due to not following the
www.thurj.org 107
access to the tanker market. Next, I construct household demand low priced tanker water, Price_Low. Both variables are binary, where
for tanker water. Due to simultaneous determination of price in Price_Low takes on the value of 1 if the tanker water cost is equal
demand and supply models, I reduce the threat of reverse causality to or less than the median price. This method addresses concerns
in the demand function by constructing the tanker water price that of reverse causality because although the quantity may determine
the household faces using household characteristics, or instrumental the price, an absolute measure, it does not determine whether a
variables (“IV”), that determine the price and do not determine the household faces a high price or a low price, a relative measure.
quantity demanded by the household. I use the constructed low The OLS model improves Equation (1) by replacing the general
price variable in the demand equation in place of the low price price variable with Price_Low. I also add to the model the interaction
variable, which robustly isolates household demand—the effect of terms suggested by the theoretical model, specifically the interaction
price on the quantity demanded. This method considers the actual of price and income and the interaction among preference variables.
price paid by the household. Quantity Consumed = β0 + β1 Price_Low + β 2 Income
I use the predicted demand to determine the level of equity in + β3 Pricce_Low * Income + β 4 Preferences
the tanker market. First, I reject the predictions of the theoretical
model by finding evidence of horizontal equity. I find the ethnic- + β5 Preferences * Preferences + ε (3)
ity variables insignificant in the demand equation, which excludes where all variables are defined as above. The elasticity of demand
discrimination as a determinant of tanker water consumption. This is defined as
result is robust to the demand specification. On the other hand, I ε D = % change in quantity given % change in price
confirm the theoretical model’s prediction of vertical inequity. I
(β1 + β3 * Income )Price
find that the poor pay more for tanker water given their household =
income than the rich, which is evidence of a regressive pricing Quantity Consumed (4)
structure. This result is robust with regard to the mechanisms house- Although this model reduces the threat of simultaneity, it does
holds use to cope with imperfect water supply, or the correlates of not eliminate the concern because the Price_Low and Price_High
consumption. dummies, though relative values, are still endogenously deter-
mined in the market. The Dichotomous Price model improves the
Methodology OLS model by exogenously identifying the price variable using
instruments to eliminate the reverse causality concerns. I use four
Constructing demand instrumental variables:
Demand for a normal good, such as water, is a function of t House Years—the number of years the household has lived
three considerations: the price; household income—their budget in the house. The longer the family has lived in the same house, the
constraint; and household preferences. I mobilize the empirical more likely they are to be established in the community and have
implications of the model in Chapter 2 to specify the demand rela- stronger social connections with local business owners, including
Economics
tionship among these factors. tanker drivers. These households face the low tanker price;
The naïve model is the simplest version of household demand t Prob Piped—the probability that the piped water comes to
for tanker water. This model simply regresses the quantity of water the household over the course of a representative day. The lower
consumed on the price of water, controlling for the household’s the probability that water will come, the greater the desperation
budget constraint and household preferences: of the household, and the higher the price that the household will
ln(Quantity Consumed ) = β0 + β1 ln( Price ) + β 2 ln( Income ) accept. Note that the probability of piped water supply is not directly
! correlated with the quantity of piped water that comes during a
+ β3 ln( Preferences ) + ε (1) particular supply period;
where Income is a vector of a household’s relevant budget constraint t Reader—whether or not the household knows their water
variables, Preferences is a vector of a household’s relevant prefer- meter reader. Knowing the water meter reader indicates how well
ences variables, and e is the common measurement error. Elasticity connected to the local community is a household. It also demon-
of demand is defined as strates the respondent’s attention to the individuals that handle the
household’s water; and
ε D = The % change in quantity given a % change in price = β1 (2) t Unskilled—whether or not the household’s working members
The results of the naïve model are threatened by simultaneity hold unskilled jobs. Unskilled workers are less likely to be in posi-
bias, which results from reverse causality between variables. Assum- tions of power within the community and thus have less pull with
ing that water is a normal good, reverse causality could arise if the the tanker drivers for favors. The families of unskilled workers,
price impacts the quantity consumed and the quantity consumed therefore, likely pay higher prices for tanker water.
impacts the price. This creates bias in the estimation of demand (DFKRIWKHVHLQVWUXPHQWVFRQVLVWHQWO\DQGHI¿FLHQWO\HVWLPDWHV
elasticity that may lead to spurious results. "#$!$%&'($%')*!+,-,.$"$-/!!"#$%&'(),FRQ¿UPE\WHVWLQJWKH
I disentangle the effect of price in the demand equation from the -$0$1,%2$!,%&!$3'($%$4"5!'6!$,2#!4%*"-).$%",0!1,-4,70$8!9#$!4%*"-):
determination of price in the supply equation by creating the price .$%"*!,-$!-$0$1,%"!7$2,)*$!$,2#!4*!*"-'%(05!2'--$0,"$&!;4"#!"#$!
variable anew. I extract from price what is meaningful to households ",%<$-!+-42$/!'-!"#$!2'1,-4,%2$!'6!"#$!4%*"-).$%",0!1,-4,70$!,%&!
but not meaningful in determining the price in the supply equation. "#$!$%&'($%')*!4%&$+$%&$%"!1,-4,70$/!!"#$%&'()/!4*!%'"!=$-'8!9#$!
The OLS method accomplishes this by separating the one supply SUDFWLFDOWHVWIRUUHOHYDQFHLVWKH¿UVWVWDJH)VWDWLVWLFZKLFKPXVW
curve into two so that demand can be determined as households 7$!,7'1$!>?8!@%!4%*"-).$%"!4*!1,04&!46!4"!4*!%'"!2'--$0,"$&!;4"#!"#$!
differentially react to the two supply curves. I separate the supply A),%"4"5!'6!",%<$-!;,"$-!"#,"!"#$!#')*$#'0&!2'%*).$*!'-!46!"#$!
of the high priced tanker water, Price_High, from the supply of the 2'1,-4,%2$!'6!"#$!4%*"-).$%",0!1,-4,70$!,%&!$!4*!=$-'8!9#$!"$*"!6'-!
!"#$!%!&'()&*)'+!),-%*!%)./*'-'&*'&0)#1)'+!)#2!3&4!%'&1(&%$)3!*'3&0'&#%) may affect the quantity of tanker water demanded if a household

WHVWZKLFKLVWKH)VWDWLVWLFFRPSXWHGXVLQJWKHKRPRVNHGDVWLFLW\ receives large amounts of water outside of the tanker and piped
#%5()r6*)4&*'3&78'&#%)9&'+)!"#)4!$3!!*)#1)13!!4#:;)) water sources. In this case, the quantity of water received by the
The Dichotomous Price model is as follows: household from the third source of water should be controlled as the
First stage: quantity of piped water is controlled. My survey includes household
level data on bottled and cooler water consumption. I included this
Price_Low = β0 + β1 House _ Years + β 2 Prob_Piped + β3 Reader water in the demand regressions and found bottled and cooler water
+β 4Unskilled + β5 Income + β6 Preferences consumption to be insignificant and non-informative. However,
many households also consume spring water. The survey did not ask
+β7 Preferences* Preferences + ε (5) households how much spring water they consume. If the omission
of household spring water creates omitted variable bias, then this
Second stage: would overestimate household demand for tanker water because
consuming spring water leads a household to consume less tanker
Quantity Consumed = β8 + β9 Price_Low + β10 Income water and be less willing to pay more for tanker water. The threat
+ β11 Prrice_Low * Income + β12 Preferences of this bias is minimal because only a small fraction of households
in the area also consumed spring water.
+ β13 Preferences* Preferences + ε (6)
where all variables are defined as above. As the Price_Low variable Testing equity
is binary, I estimate this model using the probit linear regression I use the IV with Continuous Price model, the most robust
procedure. The elasticity of demand in the Dichotomous Price is model, to test the levels of horizontal and vertical equity in the
defined as in the OLS model shown in Equation (4). informal market. First, I test horizontal equity by including ethnic-
Finally, the IV with Continuous Price model further improves on ity in the demand function, as given by the theoretical model. The
the Dichotomous Price model by using as the independent variable specification becomes
the particular price that households face. I use the same exogenous $%&'()'(*+,<
and relevant instrumental variables as in the Dichotomous Price
model, and the first and second stage regressions are also the same Price = β0 + β1 House _ Years + β 2 Prob_Piped + β3 Reader
except that the dependent variable in the first stage regression is +β 4Unskilled + β5 Income + β6 Preferences
now Price. The IV with Continuous Price model is as follows: + β7 Preferences** Preferences + β8 Ethnicity
First stage:
+ β9 Ethnicity * Income + ε (9)
Price = β0 + β1 House _ Years + β 2 Prob_Piped + β3 Reader
Economics
+β 4Unskilled + β5 Income + β6 Preferences Second stage:
+ β7 Preferences** Preferences + ε (7) Quantity Consumed = β10 + β11 Price + β12 Income
+ β13 Pricce_Low * Income + β14 Preferences
Second stage: +β15 Preferences * Preferences + β16 Ethnicity
Quantity Consumed = β8 + β9 Price + β10 Income β17 Ethnicity * Income + ε (10)
+ β11 Price * Income + β12 Preferences The null hypothesis is β16 = β17 = 0 and the alternate hypothesis
is β16 = β17 < 0.
+β13 Preferences * Preferencces + ε (8) There is ethnic discrimination in the tanker market if I reject
where all variables are defined as above. The elasticity of demand the null hypothesis, and there is discrimination against households
is defined as in Equation (4). of Palestinian ethnicity if I reject the null in favor of the alternate
The estimation of tanker water demand may be biased if there hypothesis.
are any omitted variables. Possible omitted variables include the Additionally, I check to see if the result is robust to alternate
altitude of the household’s houseplot and the quantity of water specifications of demand by determining the relationship between
received from other water sources. First, a local Jordanian mid-level ethnicity and the quantity of tanker water consumed at its most
worker in the water sector suggested that altitude directs tanker basic linear relationship with all possible interaction terms, as given
water consumption in Ayn al-Basha because the households at high- below
est altitude receive insufficient quantities of water from the piped
supply. These households must rely on tanker water to meet their Quantity Consumed = β0 + β1 Price + β 2 Family members
water needs (Interview A, 2009). I tested this effect by including +β3 Piped Water Consumed + β 4 Frequency Piped Water Supplied
the altitude in the demand regressions. I determined houseplot
altitude by interpolating from the altitude isoclines at 50-meter +β5 Income + β6 Ethnicity + β7 Price* Ethnicity
intervals in the GIS data of Emir Ali from Engicon (Engicon, 2009). +β8 Family members* Ethnicity
I found altitude to be insignificant and non-informative in the +β9 Piped Water Consumed * Ethnicity
demand regressions. Therefore, the omission of altitude does not
+β10 Frequency Piped Water Supplied * Ethnicity
bias the results.
Second, the quantity of water received from other water sources +β11 Income* Ethnicity + ε (11)
www.thurj.org 109
The null hypothesis is that β6 = β7 = β8 = β9 = β10 = β11 = 0, and water in the study area is a uniform good.
the alternate hypothesis is that β6 = β7 = β8 = β9 = β10 = β11 < 0. There
is ethnic discrimination if I reject the null hypothesis, and there is Predicting tanker use
discrimination against Palestinian households if I reject the null In order to construct household demand for tanker water, all
in favor of the alternate. observed households must be on the same demand curve. The theo-
I test vertical equity by analyzing the distribution of costs for retical model demonstrates that this occurs as long as two conditions
tanker water across the households on the basis of income. First, I are met. First, no household that uses tanker water to meet its mini-
confirm that tanker water is a normal good by analyzing the income mum survival threshold should be considered in the data set. Since
elasticity in the IV with Continuous Price model. Income elasticity is such a household would have an exorbitantly high willingness to
∂MT (β10 + β11 )Income pay for tanker water, this behavior would not accurately represent
= the normal tanker market. Therefore, all households must meet
∂( y − α min ) Quantity Consumed
(12) their minimum water needs through the piped water network.
I expect the elasticity of income to be positive. This insures that the portion of the demand curve of all households
Second, I analyze the variable role of tanker water consumption that does not increase utility—since it is below the survival level—
in a household’s budget constraint. I determine who pays the highest is piped water. Second, WTP characteristics should be the only
prices for water, absolutely and relatively. Additionally, I discuss the demographic household characteristics that explain whether or not
role of coping mechanisms in clarifying the level of vertical equity. a household uses tanker water. If a particular household character-
istic excludes a household from the tanker market, then household
Demand results demand will be biased. As long as these two conditions are met the
The informal market plays a significant role in providing house- consumption and price data from all households will construct one
holds access to water. The average quarterly total water supply is 55.9 demand curve, after controlling for WTP characteristics.
cubic meters. Forty-six percent of households use tanker water. On The first condition is met if households receive more piped water
average, tanker water constitutes 8.4% of household water supply. than the minimum quantity required for survival. Chapter 2 adopts
the assumption from Gleick (1996) that humans require at least 20L
Uniformity of tanker water of water per day for basic survival, or 1.8 cubic meters of water per
I test the assumption from the theoretical model that tanker person over a three-month period. Empirically, I find that the aver-
water is a uniform good. If tanker water is not uniform, then the age level of piped water consumption per person among households
quantity demanded should be qualified by the quality of the water, is 9.175 cubic meters for three months, with a range extending from a
as suggested by Olmstead (2010) and the World Bank (1995). minimum of 1.88 cubic meters to a maximum of 67.38 cubic meters.
Based on my field research, I predict that there is only one variety This demonstrates that all households included in the survey meet
of tanker water. Though the water comes from different springs, their minimum water needs through piped water and confirms the
Economics
the tanker drivers consider the quality of the water at these differ- applicability of the theoretical model in Chapter 2 to the situation
ent springs equivalent because they are all equally monitored by of household water demand in Emir Ali.
the government and the tanker drivers switch among the various I test the second condition by determining which characteris-
springs when filling up the tanks depending on the daily quota of tics differentiate families that consume tanker water from those
water to be sold at the springs. that do not. To determine which household characteristics, if any,
The alternate hypothesis is that there are multiple varieties of are significantly related to the use of water tankers, I regress the
tanker water. If there were more than one variety, I would expect Tanker Use dummy on all household characteristics. The Tanker Use
the better quality water to be more expensive. To test the alternate dummy is 1 if the household uses tanker water. Table 4B presents
hypothesis, I run an OLS regression with heteroskedastically-robust the household characteristics that are expected to influence water
standard errors of the per unit price of tanker water on the house- demand. None of the characteristics are significantly related to
hold’s satisfaction with tanker water, controlling for the household’s Tanker Use, indicating that there is no demand-based reason why
satisfaction with piped water. Table 3A in the Appendix presents the some households use tanker water and others do not and it must
results. All tables may be found in the Appendix online. Regression instead be related to the particular water supply conditions of a
1 includes the most relevant satisfaction variables to the perceived household.
“quality” of the water. Regression 2 includes additional satisfac- Table 4C considers whether any other household demographic
tion variables. Finally, Regression 3 includes only the aggregate characteristics are correlated with the Tanker Use dummy, including
satisfaction variables, the Satisfaction Index variables, for tanker the household’s ethnicity. The only significant coefficient is whether
and piped water. the respondent is male or female. Regression 1 suggests that when
As the table shows, the only significant predictor of the per the sex of the survey respondent is male, then the household is 15.0%
cubic meter cost of tanker water is satisfaction with the quantity of less likely to use tanker water. This is likely because males advocate
tanker water received. The significant variable describes the quantity better for the household to the local water ministry to ensure that
dimension of the uniform good and not the quality dimension, so the household’s water needs are met through the piped water. Eth-
it does not indicate that there is more than one quality of tanker nicity is included in each regression, though it is never significant.
water. The significance of the Satisfaction Index in Regression 3 This invalidates the theoretical model assumption that Palestinian
suggests that the price paid influences the perceived quality of the families are more likely to purchase water from tankers as a result
water, but Regression 4 confirms that this significance comes wholly of under-fulfilled water needs from the piped water network.
from the satisfaction with the quantity of the tanker water supplied The only significant difference between families that use tanker
as the price per cubic meter increases. I conclude that the tanker water and those that do not use tanker water is whether or not the
piped water network provides for the water needs of the household. Dichotomous Price model results
There are no demographic household characteristics that explain the The OLS model likely does not correct all of the reverse causality
distribution of household tanker water use, including ethnicity. All in the specification of demand because the variables that separate
observed households share the same demand curve because both supply, Price_Low and Price_High are still determined within a sys-
conditions are upheld. The empirical household demand construc- tem with reverse causality. The Dichotomous Price model improves
tion may proceed by the assumptions of the theoretical model. the OLS model because it instruments for the values of Price_High
and Price_Low with the WTP factors that most likely determine
Specifying demand whether a household faces a high or a low tanker price. I expect
Given the wide array of available budget constraint and prefer- this model to reduce the threat of omitted variable bias because the
ence variables available in the data to measure household demand interaction terms consider the range of omitted variables that help
for tanker water, I use the naïve model to determine which have determine tanker price.
the most explanatory power. The best model is I confirm the relevancy of the four instrumental variables indi-
vidually, and the relative exogeneity of the variables jointly. The F
Quantity Consumed = β0 + β1 Price + β 2 Income statistic is 11.055, greater than the desired 10, with a p-value of 0.026.
+β3 ln( Family members ) + β 4 Income_Low + β5 Income_Middle The J statistic is 2.18 with a p-value of 0.536, suggesting exogeneity.
+β6 Income_High + β7 Piped Water Consumed + β8Tank Volume The results from the second stage regression are presented in
Table 4E. Regression 1 and 2 are identical except that Regression 2
+β9 RooftopTank Volume + β10Tanker Satisfaction In
ndex + ε
requires the price variable to be a dummy, whereas the price variable
(13) in Regression 1 is a continuous variable over the range 0 to 1, as
predicted by the instrumental variables. I present the constructed
OLS model results demand relationships from the two regressions in Figures 4B and
The unexpected results on the direction of the demand elasticity 4C in the Appendix. Regression 1 is superior because it captures
in the naïve model confirm the concerns about the threat of simul- more of the variance in the instrumental variables than the price
taneity. As feared, the simultaneity creates bias in my estimation of specification in Regression 2.
demand elasticity that spuriously suggests positive demand elastic- All variables lose significance in both regressions except the
ity where negative demand elasticity is expected. To address the number of individuals in the household, the interaction term
simultaneity, I disentangle the effect of price in the demand equation between the household’s per capita income, and the interaction
from its determination in the supply equation. I use Specification term between price and household income. In this model, the loss of
(3) with the specific budget constraint and preferences variables significance of the independent variable suggests that the interaction
given in Specification (9). term between the income and price is more important than the role
Table 4D presents the results of the OLS model. In the naïve of the price alone in determining the quantity of water consumed
Economics
model (not presented) the demand elasticity is positive, but when the by households. Regression 1 suggests that as a household moves
model is re-specified to restrict the relationship between the price from the high price to the low price, at a certain level of per capita
and quantity to the effect of the price on quantity, the demand elas- income, the household’s demand for tanker water increases by
ticity is negative. The regression coefficient indicates that charging 0.559 cubic meters. The regressions confirm the negative demand
a household a low price increases water consumption by 6.5 cubic relationship and suggest the household’s tanker water consumption
meters than if the household were charged a high price. is highly responsive to increases in tanker price.
In Regression 1, the only significant variable is the interaction The demand elasticity suggested in the Dichotomous Price
term between per capita income and the tanker water price. The model should be interpreted as the maximum household responsive-
term suggests that given a certain level of per capita income, house- ness to changes in price because it reflects the effect on consumption
holds that face a low tanker price consume less than households of households moving from the mean high price to the mean low
that face a high tanker price. The magnitude of the coefficient on price, which is a much greater price difference than any household
this interaction term is much smaller than the price variable coef- actually faces in the market.
ficient, preserving the negative demand relationship. Moreover, the
magnitude of the interaction term shows that poorer households are IV with Continuous Price model results
less responsive to changes in price than are wealthier households, I improve the Dichotomous Price model by mobilizing the full
as predicted by the theoretical model. variation in tanker price faced by households to determine house-
Regression 2 is the complete demand specification. The price hold tanker water consumption. I use the same instruments as in
of the tanker water, captured by the Price_Low dummy, has the the Dichotomous Price model for the same reasons. I confirm the
greatest effect on the amount of tanker water that the household relevance and relative exogeneity of the four instruments using as
consumes. This regression demonstrates that the households in Emir indicators the second-stage F-statistic and J-statistic. The F statis-
Ali demand tanker water to supplement the piped water supplied tic is 14.195, well above the desired 10, confirming relevance. The
but will dampen consumption if the price is not right. Figure 4A in J statistic is 2.794, which rejects the null, and suggests that the
the appendix shows the predicted values of the natural log of tanker instruments are jointly valid. This model most successfully con-
water consumption per household against the Price_High dummy. structs household tanker water demand because it best explains the
As discussed, the demand curve shown is negative because as the variation in the independent variable, the price. Additionally, this
price increases, the quantity demanded decreases. model largely confirms the predictions of the theoretical model.
Table 4F presents the results and Figure 4D illustrates the con-
structed demand relationship. There are five significant determinants
www.thurj.org 111
of household tanker water demand. When the price increases by one is only 44. Second, the constructed model of demand fails to pre-
JD, household consumption of tanker water decreases by about 3.5 dict nearly half of the variation in the quantity demanded. This is
cubic meters. This is a considerable effect because it is more tanker shown by the R 2 value of 50%, which means that the model explains
water than the average household consumes in one month. This only about 50% of the variation in household demand. However, it
result is consistent with the traditional model of household demand is worth noting that this R 2 is on the upper edge of those in other
and with the predictions of the theoretical model in Section II. water demand models in the literature.
Additionally, with each additional family member, the household Part of the remaining 50% of unexplained variance may be due
demands about 1 additional cubic meter per month, or 1000 liters of in part to errors in variable bias. There may be measurement error
water per month. As there are returns to scale in household water in some of the variables, particularly in two variables critical to
use in terms of cooking, cleaning, gardening and other household the demand regression, income and the number of people in the
activities, it is consistent with the existing literature that a marginal household. I discussed and for the most part dismissed in Chap-
family member should only require the household to reconfigure ter 3 the possible internal validity threats to the measurement of
household water demand slightly above the level of water required household income. I concluded that the levels of household income
for daily survival (i.e. 600 liters per month). The theoretical model are relatively consistent. However, the absolute level of household
predicted the positive relationship between demand and the number income—the external validity of the data—is still questionable.
of family members. Some households probably underestimate their income due to fear
All of the variables are consistent with the predictions of the of tax repercussions or jealousy, while others likely overestimate
theoretical model, except for income. The income results will be their income out of pride. The net result does not wash away this
discussed in Section 4.3.2. in the context of vertical equity. To con- concern of errors in variable bias, but magnifies it.
firm that the elasticity differential is not caused by a difference in the In conclusion, I find that the elasticity of demand at the aver-
quantity of piped water available to households, Regression 2 adds age price and average quantity consumed is -1.5863. This suggests
an interaction term between the per capita income and the quantity that when the price increases by 1%, the quantity of tanker water
of piped water consumed. This interaction term is insignificant. demanded decreases by 1.59%, holding all else constant. The elas-
I cannot conclude whether or not the theoretical model’s pre- ticity likely changes throughout the year based on changing local
diction that household demand for tanker water decreases in the weather conditions and the complementary availability of water.
quantity of piped water consumed is true. In the first regression the This elasticity is higher than the average elasticity of demand in the
household’s quantity of tanker water consumed is increasing in the formal water market as demonstrated in the literature. Consistent
quantity of piped water that the household consumes, indicating a with the theoretical model, the elasticity is increasing in the relative
positive correlation between household consumption and demand. price of the water to the household and decreasing in the quantity
However, this effect is likely spurious because the independent effect consumed. However, the elasticity is not dependent on household
loses significance when I add the interaction term of per capita income or the quantity of piped water consumed, as predicted.
Economics
income and quantity of piped water consumed. This suggests that

there is some positive correlation between higher income house- Equity results: Horizontal equity
holds and households who receive substantial quantities of water Horizontal equity occurs when all similar individuals are treated
through the piped network. To further explore the possibility of the same—an absence of discrimination—and households are only
negative feedbacks, I include in Regression 3 a new binary variable differentiated by their willingness to pay (WTP) for a good. I con-
to capture consumption of piped water that is 1 when the household sider the level of horizontal equity in the informal water market
consumes less than the average amount of piped water in the area. by analyzing to what extent ethnicity influences water consump-
Controlling for piped water consumption, all of the coefficients on tion patterns. Table 4G presents the results of household demand
the variables interacted with piped water consumption lose signifi- that is modified to include the ethnicity terms as set forth by the
cance. However, the new binary variable has a negative coefficient, theoretical model. Regression 1 includes a dummy for Palestin-
which is consistent with the interpretation that when households ians households, while the subsequent regressions include both the
receive small quantities of piped water, tanker water consumption dummy and interactions between the ethnicity term and household
is lower, and vice versa. income, as recommended by the theoretical model. Each of the
The final determining factor warranting special attention in instrumental variables regressions maintained the relevance and
the household demand function is the tanker satisfaction index. relative exogeneity of the instruments.
In Regression 1, the level of household satisfaction with the tanker Across all of the regressions presented, the household’s ethnicity
water has the most positive and significant effect on the quantity of has no significant effect on the quantity of tanker water consumed.
water consumed by the household. This is consistent with the role It is noteworthy that the direction of the ethnicity dummy suggests
of the reliability and quality variables in the theoretical model. As that Palestinian households consume less tanker water than their
predicted by the theoretical model, the interaction term between non-Palestinian neighbors, however this effect is insignificant.
the quantities of piped water consumed and tanker satisfaction is Even if the results were significant, the coefficient in Regression
negative, albeit insignificant. 1 shows that magnitude of the effect would be trivial. On aver-
The IV with Continuous Price model is the optimal model of age, Palestinian households demand about 1.5 cubic meters less of
household demand for tanker water given the available data, how- tanker water than Jordanian households, which is half of the effect
ever it is far from a complete or perfect specification for two main of a 1JD change in price and even smaller than any of the income
reasons. First, the demand regression has a very small number effects. Additionally, including the ethnicity variable in the demand
of observations because the data includes few households with specification decreases the magnitude of the price coefficient by a
complete characteristics. The number of observations considered cubic meter and the magnitude of the coefficient on the natural log
of the number of people in the household by one-half cubic meter. 2009). There is a chance, however, that the possibility of inferiority
I check the robustness of these results by creating a new specifi- is spurious because the water supplied to the rich households in the
cation of demand. Rather than assuming the demand specification area is likely underreported in the government data.
motivated by the theoretical model, as given by the IV with Con- The possible inferiority of tanker water has incredible implica-
tinuous Price model, I assume a strictly linear relationship among tions—unforeseen in the theoretical model—on the very existence
the classic demand determinants: price, family size, quantity of of vertical equity in the tanker market. If tanker water is an inferior
piped water supplied, income, ethnicity, and all interactions with good, then households who can choose to consume water from
ethnicity. I vary the identification of the price variables as well, sources other than tankers do. This suggests that the very existence
considering the identity, square, and natural log. Changing the of the tanker market serves some social good of enhancing equity
specification allows me to see if the horizontal equity evaluation is because households with no other options for water supply turn to
hindered by the former specification. Tables 4H and 4I present the this market. Additionally, the possibility that tanker water is infe-
results: across all specifications of tanker water demand, ethnicity rior flies in the face of the common misconception among foreign
has no significant effect. water workers that only the rich use tankers. One interviewee, for
Therefore, I accept my null hypothesis that there is no dis- instance, when asked who uses tankers responded “those who pay”
crimination on the basis of ethnicity in the tanker market in Ayn (Interview P, 2009).
al-Basha. This finding rejects three components of the theoretical Regardless of the income elasticity, many households use tanker
model. First, the ethnicity variable is insignificant in the demand water to fulfill their water demand, making vertical equity an
equation. Second, the interaction term is also insignificant. Third important consideration in either case. If the good is normal, then
and finally, the aggregate demand is unaffected by the relative dis- vertical equity must be assessed to analyze the distribution of costs
tribution of household ethnicity in Ayn al-Basha. for this desirable and necessary good across the households on
the basis of income. Alternatively, if the good is inferior, then the
Equity results: Vertical equity question of vertical equity is even more important because regres-
Vertical equity occurs when individuals face a neutral or progressive pricing would be a double whammy against poor households:
sive pricing scheme, similar to the structure of progressive taxes consuming an inferior product—perhaps due to questionable quality
with a net transfer from rich to poor. Under progressive pricing, the of the good—and paying more for the good.
poor pay a lower proportion of income for water than the wealthy. In vertical equity terms, the question is whether the high-income
First, I analyze the elasticity of income to determine whether households pay a smaller fraction of their income for tanker water
or not tanker water is a normal good, as predicted by the theoreti- than do low-income households, as predicted by the theoretical
cal model. Household consumption of normal goods increases as model. Given that the first stage least-squares regressions in the IV
household income increases. I use the IV with Continuous Price with Continuous Price model explains little variation in the price, I
model to test for normalcy of tanker water but substitute the natural am unable to construct a reliable model to predict the price of water
Economics
log of the quantity variable for the variable’s identity, so income that households face. Therefore, I rely on price point comparisons
elasticity is simply the coefficient of the natural log of the income to analyze the progressivity of the tanker market.
variable. Tanker water may be one of three types of goods depend- To uncover the particular relationship among household income
ing on the value of the coefficient. A positive coefficient less than 1 and prices, I divide the households into five income brackets. The
suggests that tanker water is a normal good because the quantity average monthly income of the first bracket is 100JD, of the second
demanded increases as income increases, but less than linearly. A is 250JD, of the third is 400JD, of the fourth is 600JD, and of the
positive coefficient greater than 1 suggests that tanker water is a highest is 1000JD. Table 4J summarizes average and total prices paid
luxury good because the quantity demanded increases more than by the households in the five income brackets, both absolutely and
linearly as income increases. Finally, a negative coefficient suggests relatively—the absolute level weighted by the household’s income.
that tanker water is an inferior good because the quantity demanded According to these values, it is clear that the system is absolutely
decreases as income increases. neutral, but relatively regressive. The poorest households pay the
I find that the elasticity of income is negative, but extremely lowest price, though not significantly different from the average
insignificant. This suggests that tanker water may be an inferior prices paid by the wealthiest households (T = 0.5227). However, the
good. This is inconsistent with the theoretical model, albeit incon- poorest households pay the highest price relative to their income
clusively, which predicted the tanker water to be a normal good. In (Bracket 1 to 2, T = 2.21257; Bracket 1 to 3, T = 2.2409; Bracket 1
fact, the preferences specification model, Stone-Geary preferences, to 4, T = 2.5478; Bracket 1 to 5, T = 2.3185).
does not allow goods to be inferior. I can resolve this empirical The percentage of income used by households on tanker water
finding with the theoretical model by conceiving of qT as a number ranges between 1% and 23% of the household income. These num-
somewhere between 0 and -1 for tanker water, and not 0 as assumed bers seem to be absurdly high. However, a 2008 survey of household
in Chapter 2. The possibility that q is -1 precludes households who water use by a German consulting firm found that households spend
can avoid using the tanker water from participating in the market. upwards of 6.3% of their income to receive enough water to cover
Therefore, tanker drivers only enhance equity in the water market only 100 liters per capita per day (Sass and Brubach, 2008). The
to create inequity in the water supplied by taking advantage of the high envelope for the percentage of income required suggests that
ready market by selling suboptimal products. the income estimation has consistent downward bias. Regardless of
Moreover, the finding of tanker water as an inferior good is con- the specific value, however, the poorest households pay the highest
sistent with reports that the piped water supply outlines the local price relative to their income.
power structure or that wealthy and powerful households receive There is vertical inequity evidenced by this regressive relative
more consistent water supply than poor households (Interview M, pricing scheme. The regressive scheme most likely results from
www.thurj.org 113
quantity-restricted demand. Based on interviews with households I embraced this difficulty as a challenge, not a limitation. I came
and corroborated by this data, the amount of water that households to understand the market by carefully mapping the interactions
receive from tanker drivers is contingent on the size of their rooftop of households in my study area with water from the formal and
tanks. Yet, the amount of water that households pay for from tanker informal sectors through observation, interviews, and primary
drivers is based on the size of the tanker driver’s tank truck. Not all source data collection. This paper offers a glimpse into the elusive
households have an equal total volume of water tanks or total num- informal market, and the theoretical and empirical methodologies
ber of water tanks because household storage tanks are expensive herein developed may serve as a basis for future investigations of
(Gerlach and Franceys, 2009). Tank size increases with household the informal market in other areas.
income (T = 2.42), and so the gap between quantity received and In Section I, I provide motivation for the paper by asking to what
the quantity that should be received given the total amount paid is extent the informal market, given the failure of the formal sector,
larger in poor households than it is in rich households (corroborated can equitably distribute a precious natural resource. I find that the
by field observations of Interview W, 2009; and Odeh, 2009). In informal market in the Emir Ali neighborhood of Ayn al-Basha,
other words, poor and rich households pay similar amounts, but Jordan is an equitable distributor so long as a household’s payment
poor households receive less tanker water due to the limitation of for water is tied to consumption alone, not the consumption of oth-
smaller household rooftop tanks. ers who buy from the same supplier. Stated differently, for the most
The role of household water tank volume in contributing to part the tanker market equitably improves access to and distribution
vertical inequity suggests the issue may also be described as a tech- of water. However, when tanker drivers quote an inflated price to
nological problem that reinforces the local cycle of poverty. one household to compensate for a lower price offered to another,
The household water storage tank is just one of the many addi- the informal market exhibits vertical inequity, and the poor suffer.
tional costs of consuming water in the tanker market that comprise Section II develops a theoretical model of household demand for
the total price—the effective price—of water. Though the coping water from the informal sector as the residual demand not met by the
methods are not statistically evaluated, they are worth commenting piped water market. I assume that tanker firms are monopolistically
on briefly because they create further vertical inequity in the infor- competitive and that tanker drivers use their price-setting power
mal market. In response to suboptimal water quality, households to both discriminate against Palestinian households and charge
cited boiling water, freezing water and both boiling and freezing more to poor households. To empirically test these predictions, I
water. About 30% of the households have filters for the water from conducted a randomized household survey of 275 households in
the water storage tanks—piped water and tanker water—and an the Emir Ali neighborhood, as described in Section III.
additional 26% of households also use bottled water for drinking The empirical investigation in Section IV confirms two anteced-
and sometimes cooking. Filters range in price from 100 to 1000 ents to the empirical application of the theoretical model; constructs
JD for the initial investment and maintenance costs an average of household water demand using three specifications that indepen-
14JD every 4 months. Bottled water costs an average of a shocking dently address simultaneity in supply and demand; and finally
Economics
0.280 JD per liter, which is equivalent to 280 JD per cubic meter. determines the level of equity in the market by exploring discrimi-
In addition to purchasing household water storage tanks, house- nation and regressive pricing. I use an IV with Continuous Price
holds also respond to suboptimal water quantity conditions by model to estimate that the household elasticity of demand is -1.56, or
adjusting water consumption. One respondent shared her experi- that when the price per cubic meter of tanker water increases by 1%,
ence in the quote featured at the beginning of this chapter. Other the quantity of tanker water demanded decreases by 1.59%, hold-
households shared that they make more frequent trips to the mosque ing all else constant. The other significant predictors of household
when water supply is low or seek donations from local water stores. water demand are as predicted by the theoretical model: income,
Moreover, households with more time than money may travel to the number of people in the household, the quantity of piped water
local public springs to fill up containers with water. While these consumed, and interaction terms among these variables. I identify
coping behaviors, and many others, likely contribute to the inequity, and dismiss possible omitted variables, and conclude that the only
insufficient data exists to determine their magnitude. other threat of bias in the estimation of demand may be errors-in-
variables bias.
Third, I use the IV with Continuous Price model to estimate
Conclusion the extent to which there is horizontal and vertical inequity in the
tanker market. I find no evidence to corroborate the theoretical
“The regular type of water management in Jordan is crisis model’s prediction of horizontal inequity in the informal water
management.” market because I find that ethnicity has no significant influence on
-Leading Engineer, who has worked in the area for a foreign water consumption patterns. Additionally, I am unable to validate
consulting firm for more than fifteen years, 17 August 2009 the theoretical model’s assumption that tanker water is a normal
good. The possible inferiority of tanker water suggests that the
Through its role mediating access to goods, the informal sec- informal market may be more important to the water allocation of
tor has increasingly substantial and far-reaching implications on poor households than wealthy households. This possibility raises
household welfare. This paper aims to redirect the attention of the stakes of vertical inequity in the tanker market because the
economic practitioners in the developing world from the formal consumers in question are the most vulnerable water users in the
sector to the informal sector. I construct household demand for area. I find that the poor households pay a greater proportion of their
water from the informal market, and use the demand curve as the income for less water than wealthy households pay and receive. Two
basis to explore the informal market’s performance. The scarcity confounding factors likely create the vertical inequity: on the supply
of econometric work in this area is due in part to the a lack of data. side, tanker drivers provide water at lower prices to households in
their family network; and on the demand side, poor households have Ruijs, A., A. Zimmerman, and M. Van den Berg. “Demand and Distributional
household storage tanks of less volume than wealthy households. Effects of Water Pricing Policies.” Ecological Economics 66 (2008): 506-516.
As water scarcity continues to increase in coming years, the for- Sass, Jan, and Katrin Brubach. “Water Management Program in the Middle
mal supply will continue to fall short of household water demand, Governorates—Zarqa, Balqa and Madaba.” GFA Consulting Group, in
thus expanding the size of the informal tanker water market. The association with Engicon, 2008. Amman, Jordan.
larger the tanker market, the more important the consequences of Smith, Adam. The Theory of Moral Sentiments, edited by A.L. Macfie and D.D.
the vertical inequity in the market become. Intervening today may Raphael. Oxford: Oxford University Press, 1976.
preempt a crisis tomorrow. Strand, J., and I. Walker. “Water Markets and Demand in Central American
Cities.” Environment and Development Economics 10 (2005): 313-335.
United Nations Food and Agriculture Organization. http://www.fao.org/nr/
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Whittington, D., D. Lauria, and X. Mu. “A Study of Water Vending and Will-
“Secondary Data DATABASE.” Department of Statistics, Jordan. 6 September ingness to Pay for Water in Onitsha, Nigeria.” World Development 19, no.
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“Comprehensive Subscriber Survey of Balqa Governorate.” Dorsch Consult. Whittington, D., and K. Bal Kumar. “Coping with unreliable public water sup-
April 2007. plies: Averting expenditures by households in Kathmandu, Nepal.” Water
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Emir Ali Pilot Area Houseplots. Amman, Jordan: Engicon, 2009. Whittington, Dale, Xinming Mu, and Robert Roche. “Calculating the Value of
Gerlach, Esther, and Richard Franceys. “Regulating Water Services for the Poor: Time Spent Collecting Water: Some Estimates for Ukunda, Kenya.” World
The Case of Amman.” Geoforum 30, no. 3 (2009): 431-441. Development 18, no. 2 (1990): 269-280.
Gleick, Peter. “Basic Water Requirements for Human Activities: Meeting Basic “Monitoring Environmental Progress: Report on a Work in Progress.” World
Needs.” Water International 21 (1996): 83-92. Bank (1995).
Hajisyprou, S., P. Koundouri, and P. Pahardes. “Household Demand and “World Development Indicators Database.” World Bank. 2005. http://devdata.
Welfare: Implications of Water Pricing in Cyprus.” Environment and worldbank.org/wdi2005/Cover.htm.
Development Economics 7 (2002): 659-685.
Iskandarani, M. “Water Market Participation and Effective Water Prices in
Jordan: Globalization and Water Resources Management: The Changing Interviews
Value of Water.” Paper presented at the University of Dundee International
Specialty Conference, August 6-8, 2001. Interview A. Conducted by the researcher with a local Jordanian mid-level
Kanyoka, P., S. Farolfi, and S. Morardet. “Household’s Preferences and Willing- water worker. 10 August 2009.
ness to Pay for Multiple Use Water Services in Rural Areas of South Africa: Interview K. Conducted by the researcher with a former Minister of Water and
Economics
An Analysis Based on Le Blanc, David. “A Framework for Analyzing Tar- Irrigation. 10 August 2009.
iffs and Subsidies in Water Provision to Urban Households in Developing Interview M. Conducted by the researcher with a Western contractor who has
Countries.” Working paper, DESA, 2008. worked in the water sector for more than 40 years. 1 July 2009.
Mohamed, Ahmed Shawky, Alexander Kremer, and Manish Kumar. “Assess- Interview N. Conducted by the researcher with a Jordanian water engineer.
ing the Efficiency and Equity of Water Subsidies: Spending Less for Better 7 July 2009.
Services.” In Water in the Arab World, edited by N. Vijay Jagannathan, Interview P. Conducted by the researcher with a representative from a Euro-
Ahmed Shawky Mohamed, and Alexander Kremer. Washington DC: World pean consulting firm who conducted a qualitative household level survey
Bank, 2009. on water use in 2007. 14 September 2009.
Odeh, Nancy. “Towards improved partnerships in the water sector in the Middle Interview Q. Conducted by the researcher with one of the senior managers at
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nology, 2009. Interview W. Conducted by the researcher with the leading engineer at a foreign
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Environmental Economics and Policy, 2010. August 2009.
www.thurj.org 115
Minimum assignment problem

Olga Zverovich, ‘10
Harvard University, Department of Mathematics
“Does P=NP?” is one of the biggest open questions in theoretical computer science. An important advance
toward answering this question came in 1971, when Stephen Cook proved that a problem in NP—the Satisfi-
ability Problem, or simply SAT—has the property that if this problem is “easy” (polynomial-time solvable), then
all problems in NP are easy. Such problems are called NP-complete. As the first NP-complete problem, SAT has
great theoretical and practical significance. The Minimum Assignment Problem is a generalization of SAT that
asks about the existence of satisfying partial assignments to Boolean formulae. It is shown that the Minimum
Assignment Problem is NP-complete for 2-CNF and Horn CNF formulae, two well-known classes of formulae
where SAT is easy. The central finding is that the Minimum Assignment Problem is easy for “directed” 2-CNFs,
a class of formulae in the intersection of 2-CNFs and Horn CNFs. Finally, the Minimum Assignment Problem
for Boolean polynomials is investigated. The satisfiability/unsatisfiability problems are easy for Boolean poly-
nomials. Two generalizations are introduced—the Minimum True Assignment Problem and the Minimum False
Assignment Problem for polynomials—and it is shown that while the problems are easy for linear polynomials,
they are NP-complete for quadratic polynomials. A key result is that both problems are easy for bilinear poly-
nomials (quadratic polynomials represented as a product of two linear polynomials).
Introduction is a k-CNF, then SAT is called the k-SAT Problem. It is well-known

that k-SAT is an NP-complete problem for each k ≥ 3, while 2-SAT
In this paper, we introduce the Minimum Assignment Problem— can be solved in linear time, see Garey and Johnson [3].
a generalization of the famous Satisfiability Problem. The Minimum In Section 2, we consider a natural generalization of the SAT
Assignment Problem asks about the existence of satisfying partial Problem called the Minimum Assignment Problem. Given a CNF
assignments to Boolean formulae. We exhibit an interesting class C and an integer k, we ask whether there is a an assignment xo of
for which the problem is tractable—“directed” 2-CNFs. Boolean values to at most k of the variables that satises C, in the
We consider the Satisfiability Problem. Let X {x1 , x 2 ,#, xn } be sense that C(xo) evaluates to 1 for every assignment of values to the
an ordered set of 0–1 variables. A literal over X is either a variable undened variables. It is interesting to find classes of Boolean formu-
xi D X [positive literal] or its negation xi = 1 − xi [negative literal]. lae for which this problem is polynomial-time solvable. We observe
Denote the set of literals over X by LX. A truth assignment to X that the Minimum Assignment Problem problem is NP-complete
is a point x o ( x1o , x 2o ,..., xno ) of the n-dimensional Boolean cube even for 2-CNFs, but we propose a non-trivial polynomial-time
B n {0,1}n . solvable case, namely “directed” 2-CNFs. As a byproduct, we prove
A Boolean function is a mapping f : B n A B . There are three that a variant of the Vertex Cover Problem for directed graphs can
main representations of an arbitrary Boolean function f over X: be solved in polynomial time. This may be surprising in light of
Computer
Science
t conjunctive normal form [CNF]: C C1C2 $Cm , where each the fact that the Vertex Cover Problem for undirected graphs is
clause Ci is disjunction of some literals of X (and CiCj is the conjuc- NP-complete.
tion of Ci and Cj), In section 3, we investigate the Minimum Assignment Problem
t disjunctive normal form [DNF]: D = T1 ∨ T2 ∨ $ ∨ Tm , where for Boolean polynomials. Both, the Satisability Problem and the
each term Ti is conjunction of some literals of X, and Unsatisfiability Problem are easy (polynomial-time solvable) for
t Boolean polynomial: where each term Ti Boolean polynomials. As we will see, this follows from the fact that
is product of some variables of X, and denotes mod 2 addition. every Boolean function can be represented uniquely as a Boolean
A truth assignment xo satisfies a Boolean formula f if f(xo) = 1. polynomial. We introduce two generalizations—the Minimum
True Assignment Problem and the Minimum False Assignment
Decision Problem 1 (SAT) Problem for polynomials. We prove that both problems are NP-
Instance: A CNF C over X. complete even for quadratic polynomials. However, the problems
Question: Is there a truth assignment to X that satises C? are easy for linear polynomials. Comparing these two results, we see
that it is interesting to investigate the problems for an intermediate
Cook proved that SAT is an NP-complete problem. (Note that class of bilinear polynomials, quadratic polynomials represent-
the similar Unsatisfiability Problem is trivial for CNFs. Indeed, we able as product of two linear polynomials. Our main result is that
can pick any clause and assign any values to the variables in that both the Minimum True Assignment Problem and the Minimum
clause. If the clause evaluates to 1, we simply change the value of one False Assignment Problem for bilinear polynomials can be solved
of the variables. Thus, each CNF takes on value 0 at some point.) If eciently. The two problems are not similar within the class of bilinear
each clause in C involves at most k literals for some integer k, i.e., C polynomials: the algorithm for the Minimum False Assignment
Problem is more complicated than that for the Minimum True define a 2-CNF C = {ce : e D E} over X by the following: ce = (xi
Assignment Problem. We give solutions to the search versions of xj) for each edge e = xixj of G.
the decision problems. That is, we answer an existential question If T is a vertex cover in G with |T| ≤ k, then C is satisfied by
in a constructive way by producing a solution. the following partial assignment xT of size |T|: xiT = 1 if xi DT,
and xiT = ✴ otherwise.
Conversely, let xo be a partial assignment of size at most k satisfy-
Partial assignments ing C. The vertices corresponding to ones of x o constitute a vertex
cover To in G with |To| ≤ k.
Here we introduce a generalization of the Satisfiability Problem. A Horn clause is a clause that contains at most one negative
literal. Accordingly, a Horn CNF consists of Horn clauses only.
Definition 1 The corresponding Satisfiability Problem, Horn SAT, can be solved
A partial assignment to X = (x1, x2, …,xn) is a point in the set in polynomial time, see for example Dowling and Gallier [2].
{0, 1, ✴}n, where ✴ means that value of the corresponding variable Proposition 1 shows that the Minimum Assignment Problem is
is undetermined. The size of a partial assignment xo, size(xo), is NP-complete for Horn CNFs. Now we define an interesting class
defined as the total number of zeroes and ones in xo. of CNFs for which the problem is tractable.
For example, (0, c, 1, ✴) is a partial assignment of size two to (x1, Definition 2. A directed 2-CNF is a 2-CNF C such that each
x2, x3, x4) with x1 = 0, x3 = 1, and with undefined values of x2 and x4. clause in C has exactly one positive literal and exactly one negative
In general, if c j DC is a clause and xo is a partial assignment to X, literal.
cj(xo) is a Boolean function, since the values of all variables xi of cj
with xio = ✴ are undefined. If cj(xo) evaluates to 1 for every assign-
ment of the undefined variables, we say cj(xo) > 1 and xo satisfies cj. Our main result in this section is
Decision Problem 2 (Minimum Assignment) Theorem 1. The Minimum Assignment Problem for directed
Instance: A CNF C over X and an integer k. 2-CNFs can be solved in polynomial time.
Question: Is there a partial assignment to X of size at most k that
satisfies C? First, we observe that there is a natural one-to-one correspon-
dence between directed 2-CNFs and digraphs. This correspondence
The corresponding optimization problem is to find a minimum- will enable us to formulate the Minimum Assignment Problem for
size partial assignment to X that satisfies C, or to detect that there is directed 2-CNFs as a problem in graph theory.
no such an assignment. Consider, for example, the following CNF Given a directed 2-CNF C over X, we can construct a digraph
C = c1c2c3, where c1 = (x1 x 2), c2 = (x1 x3), c3 = (x2 x3). If x1 = 1 DC = (X, A) as follows: there exists an arc (xi, xj) in DC if and only if
then c1 is satisfied, x3 = 1 [to satisfy c2], and c3 is satisfied by x3. We ( xi ∨ x j ) ∈C . Conversely, given a digraph (X, A), we can construct
obtain a partial assignment (1, ✴, 1) of size 2 satisfying C. Setting the corresponding 2-CNF over X. We use notation V(D) and A(D)
x1 = 0, we obtain (0, 0, 1), a partial assignment of size 3. Finally, if for vertex-set and arc-set of a digraph D, respectively.
x1 = ✴ then we have a partial assignment (✴, 0, 1) of size 2 satisfying We now define a notion of a vertex cover for digraphs.
C. First we show that the Minimum Assignment Problem is hard
even for 2-CNFs. Definition 3. A directed vertex cover in a digraph D is an ordered
pair (T, F) of disjoint subsets such that, for each arc
Proposition 1. The Minimum Assignment Problem is NP- (u, v) D A(D), either
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complete even if each clause has exactly two literals, both of which (DIV1): u D T, or
are positive. (DIV2): v D F.
The size of a directed vertex cover (T, F) is defined as size(T, F)
Proof. First, the Minimum Assignment Problem for 2-CNFs is = |T| + |F|.
in NP. Indeed, since 2-SAT is solvable in polynomial time (even
in its search version), we can check in polynomial time whether a Decision Problem 4 (Directed Vertex Cover)
given partial assignment satisfies a 2-CNF (and is of the right size). Instance: A digraph D and an integer k.
Next, we construct a polynomial-time reduction from the Vertex Question: Does D have a directed vertex cover (T, F) with
Cover Problem which is known to be NP-hard. A vertex cover in a size(T, F) ≤ k?
graph G with vertex set V is a vertex subset T V such that each
edge of G has at least one of its ends in T. Equivalently, S = V \ T We relate directed vertex covers to minimum assignments.
is a independent set; that is, no edge of G has both of its ends in S.
Proposition 2. The Minimum Assignment Problem for directed
Decision Problem 3 (Vertex Cover) 2-CNFs and the Directed Vertex Cover Problem are polynomial-
Instance: A graph G and an integer k. time equivalent.
Question: Does G have a vertex cover T with |T| ≤ k?
Proof. Let a directed 2-CNF C and k be an instance to the
Given an instance (G, k) to the Vertex Cover Problem, we con- Minimum Assignment Problem. We consider the corresponding
sider vertex-set X of G as a set of Boolean variables. Further, we digraph DC and k as an instance to the Directed Vertex Cover
www.thurj.org 117
Problem. to both (DIV1) and (DIV2).

Suppose that DC has a directed vertex cover (T, F) with We define the condensation D* of a digraph D as follows: V(D*)
size(T, F) ≤ k. Using T and F, we define a partial truth assignment is the set of all strong components of D, and there exists an arc
xo to X by (S, S') in D* if and only if S, S' DV(D*), S ≠ S', and there exists an
0 if xi ∈ F , arc (u, u') in D with u DS and u' DS'. Proposition 3 suggests that
o when we look for a minimum size directed vertex cover in DC , we
x = 1 if xi ∈T ,
i may deal with the condensation DC and a subset Tr V (D*) of
∗ otherwise trivial vertices corresponding to all trivial components of DC. The
advantage is that D*C is always an acyclic digraph, i.e., it does not
Clearly, size(x o) = size(T, F) ≤ k. We show that x o satisfies C. have directed cycles.
Indeed, let ( xi x j ) be an arbitrary clause of C. Accordingly, (xi, xj) Let Tr be a vertex subset in a digraph D. A directed vertex cover
is an arc of the digraph DC . By Definition 3, either (DIV1) or (DIV2) (T, F) of D is called restricted if the set R = V (D) \ (T F F) is a
holds for the arc (xi, xj). If (DIV1) holds then xi DT, and therefore subset of Tr.
xio = 1, implying that xo satisfies C. If xj DF [the condition (DIV2)],
then x 0j = 0, and again xo satisfies C. Thus, Directed Vertex Cover Decision Problem 5 (Restricted Directed Vertex Cover)
is polynomial-time reducible to Minimum Assignment. Instance: An acyclic digraph D, a subset Tr V(D), and an integer
Conversely, suppose that there exists a partial assignment x o k.
to X of size at most k that satisfies C. We define disjoint subsets T Question: Does D have a restricted directed vertex cover (T, F)
o o
and F of V(DC) by T = {xi : xi = 1} and F = {xi : xi = 0}. It is easy to with size(T, F) ≤ k?
see that both (DIV1) and (DIV2) hold for (T, F). Hence (T, F) is a
directed vertex cover of DC with size(T, F) = size(xo) ≤ k. Thus, the
Minimum Assignment Problem is polynomial-time reducible to Proposition 4. The Directed Vertex Cover Problem is
the Directed Vertex Cover Problem. polynomial-time reducible to the Restricted Directed Vertex
Cover Problem.
By Proposition 2, it suffices to prove that Directed Vertex Cover
has a polynomial-time solution to establish Theorem 1. To accom- Proof. Let (D, k) be an instance of the Directed Vertex Cover
plish this, we rst reduce Directed Vertex Cover to a variant of the Problem. We construct the condensation D* of D, and define
problem for acyclic digraphs, called the Restricted Directed Vertex k* = n* - n + k, where n = |V(D)| and n* = |V(D*)|. Also, Tr is the set
Cover Problem. We begin with some definitions. of all trivial vertices in D*. Recall that the vertices of Tr correspond
A digraph is called strongly connected if it contains a directed to all trivial strong components of D. We may consider (D*, Tr, k*)
(u, v)-path for each ordered pair (u, v) of vertices. A strong compo- as an instance to the Restricted Directed Vertex Cover Problem,
nent in a digraph D is an inclusion-wise maximal strongly connected since D_ is an acyclic digraph.
subgraph of D. A strong component is trivial if it has exactly one First, suppose that the answer to the Restricted Directed Vertex
vertex, and it is non-trivial otherwise. For a directed vertex cover of Cover Problem is “yes”. It means the D* has a restricted directed
(T, F) of a digraph D, we define the rest of (T, F) as R = V(D) \ (T F F). vertex cover (T*, F*) of size at most k*. By definition, R* Tr, where
The following lemma will be useful for our next important result. R* = V(D*) \ (T* F F*) is the rest of (T*, F*).We define sets T and F
in D: T = {xi DV(D) : the strong component containing xi is in T*},
Lemma 1. Let D be a digraph, and let (T, F) be a directed vertex and F = {xi DV(D) : the strong component containing xi is in F*}. It
cover in D. Let u T, v F be distinct vertices of D. Then, there is is easy to see that (T, F) is a directed vertex cover of D. To compute
no (u, v)-directed path in D. the size k of (T, F), we use the fact that |R| = |R*|, where R is the rest
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of (T, F). We have |R| = |V(D)| - size(T, F) = |V(D*)| - size(T*, F*) =

Proof. Suppose u T and there is a (u, v)-directed path |R*|, implying that
P = (u = u1, u2, …, uk = v) in S. For the arc (u1, u2) the condition
(DIV1) does not hold, therefore u2 DF according to (DIV2). size(T, F) = |V(D)| - |V(D*)| + size(T*, F*) ≤ n – n* + k*.
Continuing inductively, we get ut DF for each 2 ≤ t ≤ k. In
particular, v DF. Since k* was defined as k* = n* - n + k, we obtain size(T, F) ≤ k,
i.e., the answer to the Directed Vertex Cover Problem is also “yes”.
Proposition 3. Let (T, F) be a directed vertex cover in a digraph D, Now suppose that there exists a directed vertex cover (T, F) in D
and let S be an arbitrary strong component of D. Then, S is entirely with size(T, F) ≤ k. Using Proposition 3(i) and (ii), we can define
contained in one of T, F, and R. Furthermore, if S R, then |S| = 1. disjoint subsets T* and F* in V(D*): T* = {S : the strong compo-
nent S is contained in T}, and F* = {S : the strong component S
Proof. Suppose that S has a vertex u DS \ T and a vertex v DS E T. is contained in F}. It is easy to check that (T*, F*) is a directed
By Lemma 1, there is no (u, v)-directed path in S, a contradiction vertex cover of D*. Moreover, Proposition 3(iv) implies that it is
to the fact that S is strongly connected. a restricted directed vertex cover. Finally, |R| = |R*| implies that
Suppose that S has a vertex u DS E F and a vertex v DS \ F. By size(T*, F*) = |V(D*)| - |V(D*)| + size(T, F) ≤ n* - n + k = k*.
Lemma 1, there is no (u, v)-directed path in S, a contradiction. Proposition 4 shows that it is enough to develop a polynomial-
If S R then either S E T ≠ 0 [and therefore S T] or S E F ≠ 0 time algorithm for the Restricted Directed Vertex Cover Problem.
[and hence S F]. In any case, S is disjoint from R. Vertices u and v in an acyclic digraph D are called incomparable
If D has an arc (u, v) with u, v DR, then we have a contradiction if D has neither a directed (u, v)-path nor a directed (v, u)-path.
Otherwise u and v are comparable. To prove that the Restricted vertex-set X in which distinct vertices x and y are adjacent if and
Directed Vertex Cover Problem has a polynomial-time solution, only if x and y are comparable in P, that is either x ≤ y or y ≤ x.
we first give a criterion for a set R V(D) in an acyclic digraph D We extend Definition 4 to all acyclic digraphs: the comparability
to be the rest of a restricted directed vertex cover. graph of a digraph D is defined as the comparability graph of the
poset of D. As an illustration, let us consider the following poset P
Proposition 5. Let D be an acyclic digraph, and let Tr V(D). A defined on {2, 3, 4, 6, 8} by x ≤ y if and only if x divides y. Figure 1
set R V(D) in D is the rest of a restricted directed vertex cover shows the Hasse diagram H of P, an equivalent acyclic digraph D
if and only if R Tr and R consists of pairwise incomparable [P is the poset of D], and their common comparability graph G.
vertices.
Proposition 6. The Restricted Directed Vertex Cover Problem
Proof. Necessity: The condition R Tr holds by the definition of can be solved in polynomial time.
a restricted directed vertex cover. Suppose u and v are distinct
vertices in R. By Lemma 1, D contains neither a (u, v)-directed Proof. To find a minimum size restricted directed vertex cover in
path nor a (v, u)-directed path. Thus, R consists of pairwise an acyclic digraph D is the same as to find a maximum set R Tr
incomparable vertices. that can be the rest of a directed vertex cover.
Sufficiency: Now R Tr is a set of pairwise incomparable verti- To construct such a set R, we use Proposition 5: R must be a larg-
ces. We define F as the set of all vertices in V(D) \ R that are reachable est subset of Tr consisting of pairwise incomparable vertices. Let us
from R. That is, R = {y DV(D) \ R: a directed path (x, y)-path for consider the comparability graph G of D. Recall that distinct vertices
some x DR}. Also, put T = V (D) \ (R F F). We prove that (T, F) is are incomparable in D if and only if they are non-adjacent in G.
a directed vertex cover of D. Suppose it is not, i.e., there exists an Thus, it is sufficient to find a maximum independent set S Tr in G.
arc (u, v) such that u T and v F. There are two cases to consider.
Decision Problem 6 (Independent Set)
Case 1. u DF Instance: A graph G, and an integer k.
According to the definition of F, u DF implies that there exist a Question: Does G have a independent set S with |S| ≥ k?
vertex w DR and a directed (w, u)-path P. Now, P F (u, v) is a directed
(w, v)-path, therefore v must be in F, a contradiction to v F. This problem is the complementary form of the Vertex Cover
Problem, and it is NP-complete in general. However, we have this
Case 2. u DR problem for the class of all comparability graphs of acyclic digraphs
Since v is reachable from the vertex u DR, we have v DF, a which is the same as the class of all comparability graph of posets.
contradiction. For comparability graphs, the Independent Set Problem can be
Thus, each case produces a contradiction, so (T, F) is a directed solved in polynomial time, see Golumbic [4]. Finally, the condition
vertex cover of D. that we need a maximum independent set within Tr can be easily
Recall that a finite poset [a partially ordered set] is an ordered pair P satisfied. Indeed, the subgraph G' of G induced by Tr is again a
= (X, ≤) consisting of a finite set X and a binary relation ≤ that satisfies comparability graph, so we may apply a polynomial-time algorithm
for the Independent Set Problem to G'.
(Reflexivity): x ≤ x, We have established Theorem 1.
(Antisymmetry): x ≤ y and y ≤ x imply x = y, and One may think that the Directed Vertex Cover Problem is hard,
(Transitivity): x ≤ y and y ≤ z imply x ≤ z for all x, y, z DX. since it is very similar to the Vertex Cover Problem for undirected
graphs. However, Theorem 1 and Proposition 2 imply the following
A poset P = (X, ≤) defines an acyclic digraph D = Hasse(P) called unexpected result.
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the Hasse diagram of P: its vertex-set is X, and (x, y) is an arc of
D if and only if x covers y. Antisymmetry implies that Hasse(P) Corollary 1. The Directed Vertex Cover Problem can be solved
has no directed cycles. Note that an arbitrary acyclic digraph D is in polynomial time.
not necessarily the Hasse diagram of a poset. However, an acyclic
digraph D uniquely defines a poset (V(D), ≤), the poset of D, on
X = V(D): x ≤ y for x, y DX if and only if there exists a directed (y, Boolean Polynomials
x)-path in D.
We now turn to Boolean polynomials P(x1, x2, …, xn) = T1 T2
Definition 4 . . . T , where each term is a product of some distinct vari-
m
The comparability graph of a poset P = (X, ≤) is the graph with ables of {x1, x2, …, xn}, and denotes mod 2 addition. Note that
we treat Boolean polynomials as Boolean functions (not as formal
polynomials), so x2 > x for every variable x. The following facts are
well-known, see for example Rosen [6].
Proposition 7. (i) Every Boolean function has a CNF

representation.
(ii) Every Boolean function has a DNF representation.
(iii) Every Boolean function can be represented as a Boolean
Figure 1
www.thurj.org 119
polynomial. Example 2. Let us consider a linear polynomial P = x1 x2 . .

Unlike CNF and DNF representations, the Boolean polynomial . x c, where c D{0, 1} is a constant. If c = 0 then P is called
m
representation is unique. Every Boolean polynomial defines exactly purely linear. Let xo be a partial assignment to X that satisfies P. If
one Boolean function. Thus, the Boolean polynomial representa- at least one variable in xo is undefined, then the resulting linear
tion of a Boolean function is unique if and only if the number of polynomial P(xo) is not a constant. Hence we must specify values
distinct Boolean polynomials equals the number of distinct Boolean of all variables, obtaining a partial assignment of size m. To get 1,
functions. Let f be a Boolean function of n variables. There are two we set all variables to 0 if c = 1. If c = 0 then we define xio = 1 and
possibilities (0 and 1) for the value of f at each
n
of the points xio = 0 for all i D{2, 3, . . .,m}.
in its domain. Hence, there are exactly 22 Boolean functions of n A similar situation takes place for the Minimum False Assign-
variables. Now we count the number of Boolean polynomials in n ment Problem – we have to specify the values of all variables.
variables. Each of the n variables either participates in a term or not;
thus, there are exactly 2n possible terms. To produce a particular Proposition 8. Both the Minimum True Assignment Problem
polynomial is to choose 0–1 coefficients for the 2n terms. Hence, and the Minimum False Assignment Problem for linear
2n
there are exactly 2 Boolean polynomials in n variables. polynomials can be solved in linear time.
What about satisfiability/unsatisfiability for Boolean polynomi- As the next step, it is natural to consider quadratic polynomi-
als? Every polynomial P > 0 takes value 1, and every polynomial als, that is Boolean polynomials of degree at most two. They are of
P > 1 takes value 0 at some points. This follows from the unique- the form P = Q L c, where each term in Q is of the form xixj,
ness of Boolean polynomials. Thus, the satisfiability/unsatisfiability L consists of linear terms, and c D{0, 1} is a constant.
problems for polynomials are easy. But these are just decision prob-
lems. To solve the corresponding search problem, we must find a Theorem 2. Within quadratic Boolean polynomials,
particular point that gives value 1 or 0 to P (or show that no such (i) the Minimum True Assignment Problem is NP-complete, and
point exists). We give solutions to the search satisfiability/unsatisfi- (ii) the Minimum False Assignment Problem is NP-complete.
ability problems for polynomials as an example.
Proof. First, observe that both problems are in NP. Indeed, since
Example 1. Let P(x1, x2, . . ., xn) be a Boolean polynomial. If it is a the Satisfiability Problem is polynomial-time solvable even in its
constant, then the search satisfiability/unsatisfiability problems search version, we can check in polynomial time whether a given
are trivial.If P is not a constant, then we consider two projections partial assignment satisfies a given Boolean polynomial (and is of
with respect to x1: P|x1=0 = P(0, x2, . . ., xn), and P|x1=1 = P(1, x2, . . ., the right size). Similarly, the Minimum False Assignment Problem
xn). Suppose that both P|x1=0 and P|x1=1 are constant, say c0 and c1, is in NP. Next, we show that both Problems are NP-hard.
respectively. Since P is not a constant, we must have c0 ≠ c1, and
we have obtained solutions to the both problems. (i) We construct a linear-time reduction from the Vertex Cover
Suppose now that at least one of P|x1=0 or P|x1=1 is not a constant, Problem.
say P0 = P|x1=0 > const. Then, P0 takes both 0 and 1 at some points Given an instance (G, k) to the Vertex Cover Problem, we con-
of B n<1 . Thus, we fix value of x1 as x1 = 0, and continue the process sider the vertex-set X = V(G) of G as a set of Boolean variables:
with P0. X = {x1, x2, . . ., xn}. Now we define an instance (P, k) to the Mini-
Thus, there is a linear-time algorithm to solve the search satis- mum True Assignment Problem with a quadratic polynomial P.
fiablity/unsatisfiablity problems for polynomials. Note that we use the same k as in (G, k). For each edge e = {xi, xj} of
We now turn to partial assignments. A partial assignment x o to G, we create the corresponding term Te = xixj in P, and we define
X satisfies a polynomial P if P(xo) > 1. P(x1, x2, . . ., xn) = Te1 Te2 . . . Tem 1, where {e1, e2, . . ., em}
is edge-set of G. The polynomial P can be constructed in linear
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Decision Problem 7 (Minimum True Assignment for time in m.

Polynomials)
Instance: A Boolean polynomial P over X and an integer k. Fact 1. If the answer to the Minimum True Assignment Problem
Question: Is there a partial assignment to X of size at most k that for (P, k) is yes, then the answer to the Vertex Cover Problem for
satisfies P? (G; k) is also yes.
Decision Problem 8 (Minimum False Assignment for Proof. We are given that there exists a partial true assignment xo
Polynomials) of size at most k that satisfies P. Note that each quadratic term xixj of
Instance: A Boolean polynomial P over X and an integer k. P must contain a variable, say xi, such that xio D{0, 1}. Indeed, oth-
Question: Is there a partial assignment to X of size at most k that erwise the polynomial P(xo) contains a quadratic term, and therefore
makes P > 0? it is not a constant. By our construction, the specified variables in xo
constitute a vertex cover T in G. Denoting by s be the total number
(These problems are equivalent within the class of all Boolean of specified variables in x o, we obtain k ≥ size(xo) = |T|. Thus, the
polynomials. Indeed, a partial assignment to X of size at most k answer to the Vertex Cover Problem for (G, k) is “yes”, as required.
makes P > 1 if and only if it makes P 1 > 0. However, as we will
see, they are not equivalent within the class of bilinear polynomials.) Now we prove the converse.
The optimization versions of Decision Problem 2 and Decision
Problem 3 are to find minimum size partial assignments that make Fact 2. If the answer to the Vertex Cover Problem for (G, k) is yes,
a given polynomial an identical 1 or an identical 0, respectively. then the answer to the Minimum True Assignment Problem for
(P, k) is also yes. symmetry, we may assume that R1 > 0, and therefore L1 = c1
and L2 = R2 c2. If c1 = 0 then the condition (Zero Term) holds,
Proof. Suppose G has a vertex cover T of size at most k. Using T, since L1 > 0. If c1 = 1 then L1L2 = L2 = R2 c2. To get L1L2 > 0, we
we construct a partial truth assignment x o for X as follows. When- must have R2 > 0 and c2 = 0. Thus, L2 > 0 and the condition (Zero
ever xi DT, we set xio = 0. All other components of xo are undefined. Term) holds.
Clearly, size(x o) = |T| ≤ k. It remains to show that x o satisfies P.
Since T is a vertex cover, each edge of G has at least one of its end- Now we give efficient solutions to the Minimum True/False
vertices in T. Using the definitions of P and x o, we see that each Assignment Problems.
term of P has at least one variable xi with xio = 0. Thus, P(xo) > 1.
Theorem 3. Within bilinear polynomials,
Fact 1 and Fact 2 show that the Vertex Cover Problem is linear- (i) the Minimum True Assignment Problem can be solved in
time reducible to the Minimum True Assignment Problem for polynomial time, and
quadratic polynomials, and the result follows from NP-completeness (ii) the Minimum False Assignment Problem can be solved in
of the Vertex Cover Problem. polynomial time.
(ii) This part is similar to (i). We just modify the definition of Proof. Let P be a bilinear polynomial.1 Let L1L2 be a bilinear
P, namely we set P(x1, x2, . . ., xn) = Te1 Te2 . . . Tem, where representation of P. Note that L1 and L2 are not constants, since P
{e1, e2, . . ., em} is edge-set of G. is not a linear polynomial.
(i) Suppose that xo is a solution to the Minimum True Assignment
Next, we consider bilinear polynomials. Bilinear polynomials Problem for P, that is P(xo) = L1L2(xo) > 1. We have L1L2(xo) = L1(xo)
constitute an intermediate class between linear polynomials, for L2(xo) > 1: According to Lemma 1, L1(xo) > 1 and L2(xo) > 1. Thus,
which the problems are easy, and quadratic polynomials, for which all variables in L1 and in L2 must be specified. But the variables of
the problems are hard. L1 and L2 constitute the set of all variables of P. Thus, we have the
Satisfiability Problem for polynomials, which is simple even in its
Definition 5. A Boolean polynomial P is called bilinear if it can be search version, see Example 1.
represented as product of two linear polynomials. (ii) Now let x o be a solution to the Minimum False Assign-
For example, P = x1 + x1x2 + x1x3 +x2 x3 = (x1 x2) ∙ (x1 x3) is ment Problem for P, that is P(xo) = L1L2(xo) > 0. We have L1L2(xo)
a bilinear polynomial. Before presenting our main result, we give = L1(xo)L2(xo) > 0: According to Lemma 2, there are two possibili-
some preliminary results. ties described in the conditions (Zero Term) and (Complementary
Terms).
Lemma 2. If 1 > L1L2 for linear polynomials L1 and L2 , then L1 > 1 To satisfy the condition (Zero Term) in an optimal way, we
and L2 > 1. should choose a term Li D{L1, L2} with the minimum number, m1,
of variables. It is always possible to make Li = 0 assigning appropri-
Proof. We have L1L2(xo) = L1(xo)L2(xo) > 1 for every assignment xo. ate values to the variables of Li. Indeed, if Li(0, 0, . . ., 0) = 1 then we
Recall that every polynomial P > 1 achieves value 0. Thus, L1(xo) > can change the value of one variable only to obtain 0. Recall that
1 and L2(xo) > 1 for every xo. Hence, L1 > 1 and L2 > 1. each Li is not a constant, and therefore it has at least one variable.
Let us consider the condition (Complementary Terms). We have
0 has more representations as a product of two linear polynomials.
L1(xo) > L2(xo) 1. (2)
Lemma 3. If 0 > L1L2 for linear polynomials L1 and L2, then either
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(Zero Term): Li > 0 for some i D{1, 2}, or Let L1 = Q R1 c1 and L2 = Q R2 c2, where Q is the com-
(Complementary Terms): L1 = L2 1. mon part of L1 and L2 excluding the constants c1 and c2. Applying
(2), we obtain Q(xo) R1(xo) c1 > Q(xo) R2(xo) c2 1, or
Proof. Let Li = Q Ri ci for i = 1, 2, where Q is the common
part of L1 and L2 excluding the constants c1, c2 D{0, 1}. The quadratic R1(xo) c1 > R2(xo) c2 1. (3)
part QR1 QR2 R1R2 of L1L2 must be 0; therefore at least two of
Q, R1, R2 are identically zero. As it is clear from (3), both R1(xo) and R2(xo) must be constants,
since R1 and R2 have disjoint sets of variables. If R1 > 0 and R2 > 0,
Case 1. If Q > 0 then R1 > 0 and R2 > 0. We have L1 = Q c1 and then L1 = Q c1 and L2 = Q c2. L1L2 is linear if c1 = c2, which is
L2 = Q c2, sp impossible. Thus, c1 ≠ c2, so (3) holds. If there is at least one variable
in R1 R2, then it is easy to specify values of all the variables in R1
L1L2 = (Q c1)(Q c2) = (1 c1 c2)Q c 1c 2 . (1) R2 to satisfy (3). Let m2 be the number of variables in R1 R2.
Now let m = min{m1, m2}, where the number m1 and m2 are
If the coefficient of Q, 1 c1 c2, is not zero, then L1L2 is not a defined above. It follows that to solve the Minimum False Assign-
constant, a contradiction. Thus, 1 c1 c2 = 0 meaning that c1 = ment Problem for P, we should find m variables involved in a
c2 1. Thus, L1 = Q c1 = Q c2 1 = L2 1, giving (Comple-
mentary Terms).
1. In the Supplement, we show that bilinear polynomials can be recognized in
polynomial time. We also show that all representations of a bilinear polynomial
Case 2. If Q > 0 then at least one of R1, R2 must be 0. By as a product of two linear polynomials can be constructed in polynomial time.
www.thurj.org 121
bilinear representation of P, and specify their values in such a way A promising direction for further research is to discover new
that the corresponding condition (Zero Term) or (Complementary classes of CNF formulas where the Minimum Assignment Prob-
Terms) is satisfied. As we have seen, it always can be done. lem is tractable. It is also interesting to investigate the Minimum
True/False Assignment Problems for multilinear polynomials. In
particular, it would be interesting to know whether the problems
Concluding discussion are tractable for Boolean polynomials that can be represented as
product of three linear polynomials.
There are three well-known classes of CNF formulas where
the SAT Problem can be solved efficiently: 2-SAT, Horn SAT, and
READ-2 SAT. Proposition 1 implies that the Minimum Assignment References
Problem is NP-complete within 2-CNF formulas and within Horn
CNF formulas. Our Theorem 1 gives a class in the intersection 1. S. A. Cook, The complexity of theorem proving procedures, in: Proceedings
of the classes of 2-CNFs and Horn CNF formulas for which the 3rd Annual ACM Symposium on Theory of Computing (ACM, New York,
problem is tractable. 1971) 151–178
We also investigate the Minimum True and Minimum False 2. W. F. Dowling and J. H. Gallier, Linear-time algorithms for testing the
Assignment Problems for Boolean polynomials. We prove that the satisfiability of propositional Horn formulae, J. Logic Programming 1 (3)
problems are easy for linear polynomials, but are NP-complete for (1984) 267–284
quadratic polynomials. Our main result is that both the Partial True 3. M. R. Garey and D. S. Johnson, Computers and intractability. A guide to
Assignment Problem and the Partial False Assignment Problem for the theory of NP-completeness (W. H. Freeman and Co., San Francisco,
bilinear polynomials can be solved efficiently. The two problems are Calif., 1979) x+338 pp.
not similar within the class of bilinear polynomials: the algorithm 4. M. Ch. Golumbic, Algorithmic graph theory and perfect graphs (Academic
for the Partial False Assignment Problem is more complicated than Press, New York, 1980) xx+284 pp.
that for the Partial True Assignment Problem. The proof of Theorem 5. K. G. Murty and C. Perin, A 1-matching blossom-type algorithm for edge
2 shows that the Minimum True Assignment Problem for bilinear covering problems, Networks 12 (4) (1982) 379–391
polynomials is essentially the same as the Satisfiability Problem 6. K. H. Rosen, Discrete Mathematics and its applications, Fifth Edition (The
for such polynomials. To solve its search version we may use the McGraw-Hill Co., Inc., Boston e. a., 2003) xxi+787 pp.
simple algorithm of Example 1. Our polynomial algorithm for the 7. C. A. Tovey, A simplified NP-complete satisfiability problem, Discrete Appl.
Minimum False Assignment Problem for bilinear polynomials, Math. 8 (1) (1984) 85–89
given in the proof of Theorem 2, is more involved.
Computer
Science

Development of an automated head-

fixed preparation to study the neuronal
mechanisms of motor learning in rodents
Kate Xie ‘10
Harvard University, Department of Organismic and Evolutionary Biology
The neuronal circuitry underlying motor sequences is poorly understood, in part due to the inability to record
from and modify neuronal activity in awake, behaving animals. A head-restrained rat preparation will facili-
tate the application of optical and neural recording techniques to behaving animals, while also simplifying the
presentation of sensory stimuli and the quantification of behavior. The following paper deals with the design
of a voluntary head-restrained method for training rodents. Rats were trained to self-initiate head restraint by
inserting their implanted head plates into a mounting apparatus, which would then automatically clamp the
head plates in place, thus head-restraining the rat. Rats were then trained to perform timed lever tap presses
for a water reward. Our results demonstrate that self-initiated restraint is feasible and stable. Rodents could
maintain self-initiated head fixation up to several minutes and performed precisely timed lever tap intervals for
head-fixation trials greater than ten seconds. Moreover, the head plate implants could be maintained in all rats
for at least ten months. Because head-restraint is self-initiated, this process allows for future automated training
of animals. The stereotyped lever tapping behavior provides a quantifiable behavioral assay that will be useful for
future studies involving the effects of fine circuit manipulation on execution and learning of motor behaviors.
Introduction possible similarity: prolonged stimulation of one subregion within

the whisker representation of motor cortex evoked a defensive whis-
Characterizations of movement and quantifiable behavioral ker retraction and eyelid closure reminiscent of defensive postures
paradigms have existed for well over a century. Over the same time evoked by continuous motor cortex stimulation in macaques (Haiss
period, technologies for recording neuronal activity have become and Schwartz 2005, Graziano 2006). Georgopoulous et al. suggested
increasingly sophisticated. However, the identification of neuronal that movement in primates may be encoded by populations of neu-
circuits underlying behaviors has proven to be difficult, in part rons, as evidenced by a series of averaged single-unit recordings
due to the limited application of recording techniques to awake (Georgopoulos 1986). Chapin et al. found similar evidence for the
and behaving animals. We hope to apply current techniques for population coding of movement in rodents, where microelectrode
optical neural recording and manipulation to awake behaviors arrays were implanted in rats trained to move a lever to obtain a
by training rats to perform a lever-tapping task while voluntarily water reward. Furthermore, when lever control was switched from
head-restrained, with the goal of identifying the cortical repre- forepaw movements to neuronal input, population activity success-
sentation underlying a precisely timed motor sequence. While we fully influenced lever control (Chapin et al. 1999). Given the large
have utilized our head-restraint preparation for the study of motor number of similarities between rodent and primate motor areas, the
control, we also note that our method of head-restraint is useful for study of motor control in rodents may elucidate the mechanisms of
other sensory studies on olfaction, whisking, or visual behaviors. learning and the representation of learned movements in primate
and human brains.
Current knowledge of neural motor control: primate studies We propose to study the neuronal basis of motor learning in
Much of the current knowledge of the functional organization rodents, which learn quickly and are less costly than primates, thus
of sequential motor control in the mammalian brain comes from allowing for more invasive and potentially much more informative
Neurobiology
studies of nonhuman primates (Graziano 2006, Tanji 2001). experiments. The rodent forepaw is dexterous; Whishaw and Coles
In these studies, macaques were trained to push, pull, or turn characterized the various digit and paw manipulations during food
a manipulandum while sitting still, a behavior requiring years of handling in rats, finding limb preferences and differential usage
training. As a result, the observed behavior was overtrained, and the of digits (Whishaw and Coles 1996). Rats can easily learn a lever
recorded neuronal activity reflected a strongly engrained behavior. tapping behavior within a few training sessions, allowing for the
While single-unit recording experiments in macaques are useful possibility of recording neuronal activity during acquisition of a
in determining the functional organization of motor areas with motor sequence. Lastly, a rodent model for motor control allows
regard to well-learned sequences, they are unable to identify the for future genetic manipulations of the circuitry involved in this
reorganization of neuronal networks during the learning of a task. behavior.
There is evidence that the encoding of movements in rodent
motor cortex may be similar to that in primates. Graziano noted this
www.thurj.org 123
Figure 1. Previous methods of

head-restraint and their uses. (A)
A head-fixing-apparatus for 2-photon
imaging in mice (adapted from Dom-
beck et al. 2007). A floating styrofoam
ball allows mice to maneuver in two di-
mensions while being imaged through
a cranial window. (B) A head-fixing
apparatus for juxtacellular recording
in rats trained on a lever-tapping task.
(Isomura et al. 2009)
Previous uses of head-fixation of the limbs (Figure 1). Brain motion associated with the running
The focus of several rodent head-fixation techniques thus far has condition was only 2-5 µm and mostly confined to the focal (x-y)
been to isolate movements for quantification of behavioral tasks. plane, and could therefore be corrected by software (2007).
Studies of whisking behavior in rodents have used various methods Recently, Isomura et al. successfully used a head-fixed method
of head fixation to accurately measure whisker movements (Wesson in rats to achieve juxtacellular recordings across all layers of motor
et al. 2009, Irina et al. 2009, Hadlock et al. 2007). The method of cortex during voluntary movements. Following an initial head-plate
head fixation is typically via a screw implanted in the head, which implant, head-fixed rats were trained to pull and push a lever at 1
is then affixed to a mounting device (Bermejo et al. 1998, Margrie Hz for a water reward. After learning the task, the rats underwent
et al. 2002). a second surgery, where an electrode was implanted into motor
The potential to apply methods traditionally reserved for anes- cortex for juxtacellular recording on the subsequent day (Isomura
thetized animals to head-fixed animals has not gone unnoticed, et al. 2009). Juxtacellular recording had previously characterized
however. Dombeck et al. used 2-photon imaging in conjunction neurons exclusively in anesthetized preparations; development of a
with head-fixation techniques in mice to optically record neural head-fixation apparatus was necessary to achieve the stabilization to
activity during behavior, allowing them to discriminate between support juxtacellular recording. Furthermore, neurobiocytin filling
the cortical representations of forepaw movement during movement of recorded neurons following juxtacellular recording experiments
and grooming (Dombeck et al. 2007, 2009). Mice implanted with
head plates were affixed to a stationary apparatus, while their body
rested on a frictionless Styrofoam ball, allowing for maneuvering
Neurobiology
Figure 2. Head-plate designs. (A) A permanent head-plate design. Small 1 mm holes aid adhesion of the plate to the skull. A large window in the head-plate is
centered around bregma, and allows for access to motor and somatosensory cortex. Notches on either side of the head-plate pertain to previous versions of our
apparatus and are irrelevant to the methods described in the present paper. (B) A removable head-plate design. Threaded inserts are permanently implanted into
the skull (top right), allowing for head-plates to be attached via screws to the skull. Pink areas signify areas of skull covered by dental cement, which is used to
attach threaded inserts or permanent head-plates to the skull.

Figure 3. Obtaining consistent bouts of restraint. (A) Behav-

ioral training session structure. An LED cue signals trial availabil-
ity, and ROI detection triggers trial onset. Trial durations are set at
a maximum, often 10 s, after which the cue turns off and a random
1-5 s wait interval is imposed before the subsequent trial can be ini-
tiated. (B) and (C) Rats in the apparatus, which involves the use of
pistons to restrain the animal. ROI detection over the reward spout
is used to detect the presence of the animal, in order to initiate a
trial. (D) Pooled trial durations (see head-fix periods in A) of two
rats over a three month training period.
allowed for definitive histological identification of the recorded

cell. As a result, Isomura et al. were able to electrophysiologically
characterize excitatory pyramidal cells and small inhibitory inter-
neurons, as well as identify the layers of cortex to which each cell
belonged. In addition to characterizing movement-specific cells
similar to those identified in macaques by Tanji et al., Isomura et
al. also found pre-movement, post-movement, movement-off, and
hold related neurons (Isomura et al. 2009, Tanji 2001, Tanji and neural control and learning of a timed lever-tapping task. Used
Mushiake 1996). in conjunction with optogenetic techniques, we hope to correlate
neural activity with behavioral output during learning. Unlike
Potential applications of head-fixation: optical manipulations previous head-fixation techniques, rats will voluntarily head-fix
Pioneering experiments suggest that photostimulation of neu- themselves and perform precisely timed lever presses to obtain a
rons expressing channelrhodopsin is feasible, suitable for long-term water reward. Rats that voluntarily head-fix themselves will provide
circuit manipulations, and can modify behavior. Ayling et al. have easy experimental access to motor cortex and an opportunity to gain
used channelrhodopsin photostimulation to create a map of motor an accurate representation of the functional role of motor cortex
cortex in transgenic mice (2009). These maps were created from laser during the acquisition and learned phases of a behavior.
stimulation of anesthetized mice with sealed cranial windows. By There are 2 specific aims of this study:
using a scanning laser procedure, they were able to obtain cortical 1. Design a method for voluntary head-fixation.
maps at speeds about two orders of magnitude faster than typi- 2. Develop a behavioral task appropriate for the head-fixed
cal electrode techniques (2009). Furthermore, because they used context.
noninvasive light stimulation in combination with sealed cranial
windows, they were able to conduct stimulation experiments 7-10
days apart on the same animal (2009). Another experiment by Results
Huber et al. combined channelrhodopsin stimulation of mouse
barrel cortex with a nose-poke task (2008). Mice were trained to
poke their noses into a left port if stimulated or a right port if not Aim #1: A method for voluntary head-fixation
stimulated in barrel cortex. All animals were able to reliably perform To distribute torque on the head implantation, we opted to utilize
this task, indicating that channelrhodopsin excitation can drive head-plates instead of head-screws to mediate head-fixation. Figure
changes in behavior in awake animals (2008). 2 shows two head-plate designs. One version incorporated 1 mm
The potential to merge channelrhodopsin stimulation with a diameter holes to increase surface area of the plate for better adher-
Neurobiology
head-fixing method rests in its noninvasive method of photostimu- ence to the skull (Figure 2a). A large opening in the center of the
lation, which allows for long-term experiments without damaging head-plate allowed for access to motor cortex after the head-plate
the brain, speeds at which experimental manipulation can occur, was implanted. A later version of the head-plate, shown in Figure 2b,
and the ability to affect behavior. Head-fixing would offer further was modified to be removable, allowing new designs to be rapidly
opportunities to increase the specificity of neuronal excitation: in tested. Three small holes allow the head-plate to be attached, via
addition to the ability to selectively express channelrhodopsin in three screws, to brass threaded inserts permanently implanted on
neuronal subtypes, light stimulation can be targeted to specific the rat (see Methods for details).
areas. Two rats were implanted with permanent aluminum head-plates,
while another rat was implanted with the threaded-inserts. Remark-
Goals and objectives ably, all three rats retained their head-plate implants for the entire
The present paper aims to use head-fixation to assay the 10 month duration of the experiment. The success of our head-plate
www.thurj.org 125
Figure 4. Progression of a consis-

tent head-restrained behavior. Per-
centage of all initiated trials classified
into three duration periods: 0-5 s, 5-10
s, and greater than 10 s, for one rat over
58 training sessions. The data present-
ed spans a time period of 10 weeks of
training, with significant breaks (week-
ends) separated by dotted lines. Some
weeks contain more sessions than
other weeks because the animal was
trained twice per day on several days.
The solid line indicates a one month
break between training sessions, where
the animal received no training. Aster-
isks indicate sessions represented in
Figure 6.
implants was likely due to a combination of several factors: maximi- of maximum trial length, and by the amount of time necessary
zation of head-plate mounting contact with skull area, implantation for the proposed optogenetic manipulations. While the rats were
of fully grown rats, and also our method of voluntary head-fixation. capable of maintaining contact with contact sensors for periods
The final version of our apparatus for head-fixation required rats up to several minutes when trial durations were not constrained
to insert their attached head-plates into a slot following the onset of (data not shown), we were more interested in obtaining a consistent
an LED signal (Figure 3). The behavioral task is described in Figure behavior to increase the number of useable trials for optogenetic
3a. Full extension of the head into the slot, as confirmed by image stimulation experiments.
region of interest (ROI) detection (see Figure 3c), triggered the Figure 3d shows the pooled results of training for two animals.
descent of air-pistons on either side of the head-plate, thus securing The imposition of a maximum trial length reduced long trial dura-
the head-plate in place. The amount of force on the head-plate was tions (> 20 s) while increasing intermediate trial durations (5-15
sufficient to constrain movement, but not so forceful as to prevent s). Trials lasting longer than maximum head-restraint duration
the rat from releasing itself. Rats could thus terminate a trial by occurred because rats would remain in the apparatus after piston
removing themselves from piston clamp, otherwise the trial would release.
automatically terminate after a specified maximum time, usually Figure 4 reveals the shift towards longer, more consistent head-
10 s. The maximum trial length was decided by a combination restrained periods over the course of training for one rat, and
of factors: the comfort of the animal, consistent reproducibility Figure 5 shows two complete sessions, early and late in the training
Neurobiology
Session 26 Session 54
Proportion of trials >10 s = 2.8% Proportion of trials >10 s = 17.3%
Proportion of trials 5-10 s = 26.7% Proportion of trials 5-10 s = 22.3%
Figure 5. Increased head-restraint durations over time. Graphs plot the trial duration versus trial number for an early session and a late session. Trial dura-
tions greater than 10s indicate that the rat either entered before the cue turned on, or remained after the end of the trial.

period, in greater detail. Some session-to-session performance vari-

ability appeared to be correlated with breaks in training periods:
performance tended to decrease during the first session immediately
following weekends, during which the rats were allowed access to
water adbitum. Although there is some variability in performance
from session to session, a trend towards increased trial durations
greater than 10 s occurs, coupled with diminished intermediate
trial lengths between 5-10 s, indicating that our modified behav-
ioral paradigm gradually shifted head-restraint periods towards
10-15 s durations, which fall well within the range of time needed
to stimulate neurons expressing channelrhodopsin and monitor
resultant behaviors (Ayling et al. 2009).
Although the trained head-restrained behavior allotted sufficient
time for optogenetic techniques, was it sufficiently stable to allow for
precise targeting of cortical areas? To answer this question, we used
a camera to capture head-plate motion over several head-restraint
trials (results shown in Figure 6). Even though piston strength
was not great enough to prevent animals from retracting them-
selves from piston hold, the pistons substantially limited head-plate
motion. Because the resolution of our camera was equivalent to 50
μm per pixel, we can only conclude that head-plate motion was less
than ± 25 μm, although head-plate motion was likely much less in
actuality (Figure 6b). These results are potentially comparable to
brain motion measured by Dombeck et al., which was 2-3 μm and
sufficient for 2-photon imaging (2007). Channelrhodopsin stimula-
tion of distinct cortical areas requires less precision than 2-photon
imaging: the beam width of stimulation used by Ayling et al. was
170 μm wide, and dendritic arbors of layer 5 cortex neurons are
estimated at 300 μm across (Ayling et al. 2009). Thus, the amount
of head-plate motion in our apparatus is small enough to allow
photostimulation techniques.
Aim #2. Development of a behavioral task appropriate for the

head-fixed context: timed interval tapping
Training a behavior in a head-restrained context differs from
training a behavior in a freely moving context in that there is
minimal physical separation between behavioral task and reward.
Separation of task and reward allows for a clear distinction between
task trials: consecutive trials are naturally divided between reward
periods. It is difficult to segment a period of head-fixation into
discrete behavioral trials without an additional cue signaling
the beginning of a new trial. Rather than implement a discrete
sequenced behavior, such as a two tap sequence, we decided to train
rats on a timed interval tapping task, which is described in Figure
7a. Rats were shaped to produce lever-taps within a range of time
intervals, with maximum reward at the specified target interval.
Rats were first rewarded for any lever press and then trained to
produce precise intervals between taps, or inter-tap intervals, which
Neurobiology
Figure 6. Pistons effectively head-restrain animals. (A) Head-plate mo-

tion over trial time, for 4 head-restrained trials in one training session. An
overhead camera filmed head-plate motion. Traces were aligned at the time
of piston release (10 s), and motion was measured with respect to a reference
image at 9 s. Piston pressure throughout the trial is shown in the top graph; at
pressures greater than 19 psi, the pistons are in contact with the head-plate. (B)
Expanded view of head-plate motion during head-restrained period. (C) View
of apparatus, including camera used to gather motion data and pistons used to
retrain animals. During motion analysis, the camera was positioned directly
over the head-plate.
www.thurj.org 127
were rewarded based on a linear reward function, described in this analysis for two rats over the same training sessions depicted
Figure 7b. The range of rewarded inter-tap intervals was gradually in Figure 8.
narrowed throughout the course of training. Both rats trained on Inter-tap times tended to increase throughout a head-restraint
this task learned to tap the lever while head-restrained. Figure 7c period (Figure 10b, f). Because the distribution was skewed towards
shows snapshots of a rat simultaneously head-restrained and lever- long inter-tap intervals, the median may be a better indicator of the
pressing. To motivate rats to maximize time spent head-fixed for center of the inter-tap interval distribution and is therefore shown
the entire duration of the trial, we shortened training sessions from in Figure 10c and g. Further analyses were conducted on the mean
hour-long sessions to twenty-minute sessions. Occasionally, rats (Figure 10d, e, h, i). Inter-tap intervals that occurred early in a
were trained multiple times per day to obtain sufficient quantities head-fixed trial were significantly shorter than those occurring at
of water. late trial times (Figure 10e, Student’s T-test, p<0.0001; Figure 10i,
Two rats were trained on the interval tapping task; both were Student’s T-test, p<0.0001).
initially trained with a 500 ms target interval, then one was switched Although Rat 2 was trained on a longer target inter-tap interval
to learn a 650 ms target early in the training period. Figure 8 shows than Rat 1, it performed faster inter-tap intervals overall, throughout
the gradual shifting of median inter-tap interval throughout train- the entirety of a trial. However, both rats shared the same minimum
ing. By the end of training, one rat’s median inter-tap interval reward boundary. While Rat 1’s inter-tap intervals approached the
approached within 100 ms of the 500 ms target. While the other target interval towards the end of a trial, Rat 2’s inter-tap intervals
rat showed a similar trend, with median inter-tap intervals greater fell short of its target interval, but became consistently higher than
than 400 ms at the end of training, it did not closely approach the the minimum reward range (Figure 10f). It is possible that the two
650 ms target interval. rats use different strategies to obtain water reward: Rat 1 may have
The mechanism of the shift towards longer inter-tap intervals maximized reward size, while Rat 2 may have maximized number
was not readily apparent in the distribution of tap timings produced of rewards. Because a sizeable proportion of Rat 1’s inter-tap inter-
during a single training session (Figure 9). The distribution of intervals fell near the target interval, it received the full spectrum of the
tap intervals appeared to be uniform within a session, although the graded reward and therefore could utilize reward size as feedback
median inter-tap interval shifted from session to session (Figure to optimize its inter-tap intervals. In contrast, Rat 2’s inter-tap
8, compare Figure 9a and b). To further investigate mechanisms interval distribution initially overlapped much less with the reward
by which learning might occur, we examined the distribution of distribution. Therefore, it rarely received the maximum reward. As
inter-tap intervals with respect to the occurrence of the first tap of a result, reward size could have been construed as binary feedback
a head-fixed period (Figure 10a). Figures 10b-i show the results of rather than graded feedback. This may be a reason why the center
Neurobiology
Figure 7. Design of a lever-tapping task within the context of head-restraint. (A) Behavioral task structure. All temporal aspects of the task are identi-
cal to that described in Figure 4a, except for the reward mechanism. (B) An analog reward system, where the reward amount is linearly dependent on inter-tap
interval (see A). The maximum reward was fixed at 40 μl. The target, minimum, and maximum rewarded intervals varied throughout the training session. In this
example, the target, minimum, and maximum rewarded intervals are 500, 350, and 800 ms, respectively. (C) Rat performing simultaneous head-restraint and
lever-tapping behavior.
Figure 8. Median inter-tap intervals approach a targeted interval over several training sessions.
Graphs plot the median inter-tap interval over several training sessions for two rats. Linear regression lines and corresponding correlation coefficients.
Session #5 Session #15

Neurobiology
Target = 500 ms Target = 500 ms

Reward Range: 200-1300 ms Reward Range: 350-800 ms
Median = 385 ms Median = 438 ms
Figure 9. Inter-tap interval distribution within one training session. Graphs plot the inter-tap interval versus time course of one session for Rat 1, early in
the training period (A) and late in the training session (B).
www.thurj.org 129
Figure 10. Inter-tap interval distribution within a trial for two rats.
(A) Trial structure and clarification of variables used in the following data analysis. (B)-(I) Summaries of the distribution of inter-tap interval intervals produced
during each trial, where trial time is calculated with respect to the time of the first tap (see A), for two rats trained on 500 and 650 ms target delays. Change in
median (C and G) and mean (D and H) inter-tap intervals over the course of a trial are shown. (E) and (I) Mean inter-tap interval significantly differs between
early (3-5 s) and late (8-10 s) trial times (Student’s T test, double asterisks indicate p <.0001)
of Rat 2’s inter-tap interval distribution was closer to the minimum et al. 2008). We show evidence that the rat may also be a good
reward inter-tap interval than the target interval, even during late candidate as a model organism for the study of motor control: rats
trial times. Regardless, the significant increase in mean inter-tap were able to coordinate precise lever-tapping behavior with self
interval from early to late trial times for both rats suggest that they head-restraint behavior. Rats can quickly acquire a lever-pressing
may be using online feedback to modify their behavior within a behavior in the context of head-fixation over a period of less than
trial (Figure 10e, i). a month. In contrast, primate models of motor behavior require
years of training and are thereby restricted to studies of the neuronal
representation of overtrained behaviors. Rodents’ faster training
Discussion periods provide an opportunity for future studies investigating the
changes in underlying neuronal representation during acquisition
Neurobiology
Our method of head-fixation will greatly facilitate targeted opto- of motor behaviors.
genetic stimulation experiments; our piston apparatus substantially
decreases head-plate motion to levels that allow reliable stimulus Learning timed motor behaviors
targeting for optogenetic manipulations. Behaviorally, we found The behavioral paradigm we presented to rats shaped a con-
that rats can be trained to voluntarily initiate head-fixation and tinuous rather than discrete lever tapping behavior. While initially
learn a timed lever-tap task while head-restrained. intended to simplify the task by minimizing the number of cues
needed to signal time points during a trial, our continuous interval
Rodents as a model organism for the study of motor control tapping task inadvertently led to the unexpected opportunity for
The rat has been most popular as an animal model for behavioral learning, via online feedback, to modify behavior within a single
studies in the context of whisking and olfaction. The majority of head-fixed trial. Both rats appeared to use online feedback to modu-
rodent studies thus focus on sensory perception in rats (Diamond late their behavior (Figure 10), but Rat 2’s inter-tap intervals did not
approach its longer inter-tap interval target as closely. To determine male Long-Evans rats. Animals were handled initially to become
the reason why it may be more difficult to learn longer inter-tap familiar with experimenter handling. After head-plate implanta-
intervals, further experiments can be done with an online shifting tion and recovery, rats were water deprived for 24 hours and then
reward distribution to more strongly favor the targeted interval and trained to obtain a water reward by pressing their head-plates
also to promote gradual shifts to longer intervals. against metal posts, which simulated a sensation of head restraint.
After several weeks, animals were placed into the cage contain-
Voluntary self-restraint ing the head-restraining apparatus, where they were trained to
Our method contributes additional improvements to current insert their head-plates into a fitted slot. Because we simultaneously
head-fixation studies: first, an automated head-restraint technique, trained animals and designed a head-fixing apparatus, the time
and second, a new philosophy—voluntary head restraint. The courses of training periods were determined mainly by the stage of
automation of head restraint will allow for large-scale training of development of the head-restraining apparatus. Animals received
animals and minimize time expended by the experimenter to train on average 5 mL of water per day while performing the task; they
animals. By using image ROI detection, we were able to reliably would also obtain access to water following the experiment if they
initiate periods of head restraint automatically. Because the pressure performed poorly. Additionally, they were given free access to water
exerted on head-plates by the pistons was minimized, automated two days out of the week.
head restraint was safe, and we report a longer head-plate implant
lifetime than all previous studies to our knowledge. Head-plate design
Our method of voluntary head-restraint introduces a novel Head-plates were designed using CAD software available from
approach to head-fixation, which has typically been accomplished by an online machine shop (http://emachineshop.com), and were
gradual acclimatization of the animal to the restraining apparatus. manufactured from 1.2 mm thick aluminum sheets. Removable
We extrapolated Isomura et al.’s idea of voluntarily initiated move- head-plates were attached, via standard 2-56 screws, to threaded
ments to include head-restraint as a voluntarily initiated movement inserts (McMaster-Carr, USA: part number 93365A112). Both
(Isomura 2009). We thus approach head-restraint as a behavior that head-plate versions include a large window in the middle of the
can be trained, rather than as an experimenter-imposed condition. head-plates for access to motor and somatosensory cortex.
Self head-restraint simply becomes one element of the action syntax
that our animals are required to learn. Head-restraining apparatus
Future studies could expand upon our head-fixation and train- All versions of the head-restraining apparatus were built
ing techniques. We have already demonstrated that rats can initiate along with Adam Kampff. The apparatus was first designed using
head-fixation, but we did not explore a full range of techniques to Google SketchUp (http://sketchup.google.com). Pistons used for
terminate a head-restraint period. The use of force sensors, the head-restraint were purchased from McMaster-Carr (Part num-
addition of another “pistons-off” lever, or the omission of lever- ber 6498K115). The lever was obtained from Cherry Electronics
tapping for a certain time period represent some means by which (Part number E33-50KL). Small cameras used for ROI detection
an animal may be trained to communicate its desire to end a head- were obtained from supercircuits.com. Software used to control
restrained period. our experiments was programmed in LabView (National Instru-
ments, USA).
Applications of our head-restraint technique
The establishment of a method of head-fixation has implications Surgical techniques
beyond the field of motor control. The majority of head-fixation Rats were anesthetized under isofluorane anesthesia. An inci-
studies thus far have utilized head-fixation to facilitate delivery of sion was made longitudinally along the top of the head to expose
a sensory stimulus. Our voluntary restraint and head-plate designs the underlying skull. Forceps were used to remove the membrane
offer new approaches to these head-restraint techniques, and can covering the skull. Using a dental drill, ridges were created in the
facilitate animal training and increase head-implant longevity. bone to increase surface area of skull for adhesion. The dental drill
Our head-restrained, lever-tapping behavior was optimized for was then used to drill six holes into the skull, three rostrally and
targeted optogenetic manipulations of motor areas. The amount of three caudally, avoiding the area overlying motor cortex. Six self-
head-plate motion observed allows for specific laser targeting for tapping stainless steel 1 mm bone screws were screwed into these six
channelrhodopsin stimulation, and the 10 s trial period comfortably locations, and a thin layer of superglue was applied to the juncture
allows sufficient time to use this fast technique and observe subse- between the skull and bone screws. It was important to minimize
quent changes in behavior (Ayling et al. 2009). These studies would the size of drilled holes by one clean penetration of the dental drill
Neurobiology
have the potential not only to define the roles of subpopulations for strongest affixation of the bone screws to the skull. The skull was
of neurons within motor areas, but also to provide targeted direct left for twenty minutes to dry before a thin layer of luting cement
manipulation of neuronal circuits in awake and behaving animals. (RelyX Luting Plus) was applied to the skull at areas surrounding
the screws. Subsequent layers of dental cement were applied, with
fifteen minutes of drying time in between each layer, until the level
Materials and methods of dental cement matched the tops of the bone screws. At this point,
either permanent head-plates or threaded inserts were cemented on
top of the bone screws. Rats were administered 10 mg/kg ketofen
Animal care analgesic subcutaneously immediately following surgery and every
All animal protocols used in this study were approved by the 24 hours for the first 48 hours post-surgery. A total of four days
Animal Care and Use Committee. All rats in this experiment were was allowed for recovery.
www.thurj.org 131
Data analysis Haiss F, Schwarz C. 2005. Spatial segregation of different modes of move-
All behavioral analyses were performed in Matlab and Microsoft ment control in the whisker representation of rat primary motor cortex. J.
Excel. Head-plate motion analysis was conducted in ImageJ. Neurosci. 25:1579–87.
Huber, D., L. Petreanu, et al. (2008). Sparse optical microstimulation in barrel
cortex drives learned behaviour in freely moving mice. Nature 451(7174):
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Neurobiology

Volume 3 Issue 2 | Fall 2010 ONLINE ABSTRACTS
Available online at www.thurj.org
A comparison of the discrete stocastic and continuous models of

antibiotic-resistant bacterial epidemics in hospitals: Implications for
modeling the impact of intervention strategies
Gordon Liao ‘11, liao@fas.harvard.edu
Past studies have modeled the spread of antibiotic resistant pathogens using continuous models (Lipsitch, Bergstrom and Levin,
2000; Bonten, Austin, and Lipsitch, 2001; Webb et al., 2005). A major limitation of using a continuous model, however, is that it fails to
consider the important role that random variations (stochastic events) play in small populations. This paper compares and evaluates
the validity and outcome of a continuous model with its discrete stochastic counterpart. In this study, Lipsitch, Bergstrom and Levin’s
continuous deterministic model of antibiotic resistance was transformed into a discrete stochastic model. Both the discrete stochastic
and the continuous models indicate the persistent transmission of resistant bacterial strain in large population sizes. However, in small
population sizes, the discrete stochastic model predicts the elimination of resistant bacteria strains as time elapses while the continuous
model does not. Consequently, interventions that do not have a permanent effect at large population levels can have a significant effect in
hastening the clearance of resistant bacteria strain in small communities. Implications on intervention strategies are further investigated.
Characterization of the effects of the gp120 V3 loop on HIV-1 resistance to

vicriviroc, a small-molecule CCR5 antagonist
Nico Lewine ‘10, nlewine@gmail.com
A new class of anti-HIV therapeutics has been developed which target CCR5, a chemokine co-receptor used by HIV-1 to enter target
cells. The HIV-1 envelope glycoprotein is responsible for mediating HIV entry into target cells, including its interaction with CCR5.
We have previously described a subtype C clinical isolate with high-level resistance to the small-molecule CCR5 antagonist vicriviroc
(VCV), and we have shown that this resistant isolate is able to use CCR5 in its drug-bound conformation. Furthermore, we showed
that a highly variable region of envelope called the V3 loop was sufficient to confer the observed resistance. It remained unclear, though,
whether conserved regions outside of the V3 loop contributed significantly to resistance. To address this question, chimeric envelopes
were created in which the V3 loop of the resistant or susceptible virus was substituted into diverse envelope sequences. The results showed
that the resistant V3 loop was able to confer VCV resistance to all of the diverse envelopes. These results, which had not been previously
demonstrated, suggest that the V3 loop of the resistant virus is sufficient to confer VCV resistance, but that surrounding regions of
envelope can modulate the magnitude of this resistance.
A search for companion stars to Type Ia Supernova progenitor dwarfs

Umang Shukla ‘11, ushukla@fas.harvard.edu
Type Ia Supernovae (SNe Ia) are thought to occur when a white dwarf attracts mass and approaches the Chandrasekhar limit, leading
to carbon ignition and detonation of the star. The preferred model from SNe Ia creation involves a single degenerate object accreting
mass from a nearby companion star. If the single-degenerate model is shown to be the exception rather than a rule, the homogeneity of
SNe Ia would be called into question, and their use as standard candles on the cosmic distance ladder would be jeopardized. A recent
paper by Kasen (2010) indicates that the blast wave from a single-degenerate supernova would compress the white dwarf’s companion
star, resulting in an identifiable blackbody spectrum at early times. Motivated thus, we analyzed 185 supernovae lightcurves compiled
by Hicken et al. (PI Kirshner 2009) for evidence of this blackbody signature. From this sample, we identified a mere 14 objects with
sufficient data quality to test this hypothesis. Thus, our results are inconclusive; as supernova detection and observation is driven by a
cosmological need for each object’s maximum light, we have insufficient observations prior to maximum light to test our hypothesis.
Our study indicates that upcoming observational surveys should be geared towards early detection of supernovae prior to maximum
light, with high cadence observations taken in the U- and B-bands in particular.
www.thurj.org 133
FEATURE Volume 3 Issue 2 | Fall 2010
By Jen Gong ‘12, THURJ Staff
T he hallways winding around the third floor of the

Center for Government and International Studies’s
Knafel building are something you won’t find anywhere
Professor Gary King, the director and founder of the
IQSS, puts it this way: progress in the social sciences used
to be largely the result of individual efforts. Now, with the
else at Harvard. The walls, lined with white boards, can revolution in information technology and the growing
literally be written on. The residents of Harvard’s Institute resources available, there are incredible amounts of infor-
for Quantitative Social Sciences (IQSS) take full advan- mation we can gather that many people will have a use for.
tage of this, and equations and ideas are often jotted down “The idea of this place is not only to sit in your office and
!
think great thoughts or prove mathematical theorems,
which happens plenty, but you come out into the hallway
Whereas social scientists and you talk to others, and you work on things together,
and you write on the walls,” King explains. “It used to be
used to only be able to study that the way to do social science was to go to the library.
the questions... ‘we’re switching Now it’s becoming a team sport.”
Although social science problems have always been
to the time where social important and incredibly difficult, researchers did not
scientists can actually solve have access to the data they needed. As King says, “the
exciting thing about this field right now is not only that
problems.’ we have the hardest questions, but we are actually getting
the data with which to address them.” Previously, social
on the walls during long discussions in the hallways. Sur- scientists would only be able to draw data from surveys,
rounded by the Weatherhead Center for International which were limited by the available population and fund-
Affairs, the Department of Government, and the Center ing. The popularity of the Internet, however, has made the
for American Political Studies, the IQSS gives people thoughts, feelings, and opinions of the members of the
from all different sectors of the social sciences a place to online community available for analysis. Whereas social
gather and tackle questions collaboratively. scientists used to only be able to study the questions,
Volume 3 Issue 2 | Fall 2010 FEATURE
King explains, “we’re switching to the time where social would not have been able to distribute health care to all
scientists can actually solve problems.” One of the major 50 million people at the same time, King and his col-
roles of the IQSS is pooling resources, including massive leagues convinced the responsible division of the Mexican
collections of servers and open-source software projects, government to allow them to give it to select randomized
and “providing the infrastructure that makes it possible to communities a year earlier than expected. Because of this,
take advantage of the data and develop different methods King says, “we got to figure out what the actual effect of
and better theories to deal with it,” according to King. the program was. We got to figure out when the program
Many of the problems we might normally categorize as worked, we got to figure out what they could do better,
purely medical or biological are also social and behavioral so when the other group got it, they could actually get a
problems. Social scientists, King says, ask the question better program.”
why people often do not follow advice that would ben- Addressing statistical questions in the social sciences
efit them. In addition to the increased volume of data, as the IQSS does thus provides governments and orga-
research in the social sciences is also gaining momentum nizations with more information about how effective
because questions in the natural sciences are converging the programs they fund are, and how to make them
!
with those of the social sci- better. However, negotiating with
ences. King cites the human groups that may have conflicting
genome project as an exam-
Social scientists, King short-term interests sometimes
ple: in addition to the data says, ask the question why poses difficulties—just one of
collected about a person’s
phenotype and explanatory
people often do not follow many problems social scientists
have to face. For example, in the
variables, they also collect advice that would benefit natural sciences, researchers can
other information similar to often manipulate experiments to
what social scientists would them. help control certain variables and
be interested in. “Those kinds of analyses are very much change others. In the social sciences, however, data is often
social science statistical analyses.” drawn from many different sources in an uncontrolled
For example, in a paper published in !"#$%&'(#)$in environment, making it difficult to isolate the variable
2009, King and others described the use of statistical researchers are interested in. “Social science problems are
methods to measure the effectiveness of a universal health much harder than others,” King says. “Imagine you were
insurance program in Mexico. This program, called in astronomy and planets, when you looked at them, got
Seguro Popular, sought to give 50 million uninsured embarrassed and hid from you. Or imagine mice could
Mexicans quality health coverage. Since the program write the rules by which biologists experiment on them.
Illustration by Sam Mendez
www.thurj.org 135
That’s our problem.” around,” Blackwell comments.

Matt Blackwell, a fifth year graduate student in gov- Blackwell’s interest in the field came from taking a
ernment and an affiliate of the IQSS, works with King on statistics class for political science at the University of
some of these problems: missing data and measurement California, Los Angeles, as an undergraduate. His inter-
error. He also runs the interdisciplinary workshop IQSS est led him to ask his professor, one of King’s former
offers for social scientists interested in applications of students, if there was any work he could help with, which
statistics and contributes frequently to the online blog. eventually led him to the Institute and Harvard. That kind
The workshop, as King describes it, is about bringing of experience is what leads Professor King to emphasize
together people from entirely different fields who have the importance of undergraduates “getting a seat at the
similar statistical questions to answer: “So we’ll have an table.” The Institute for Quantitative Social Sciences seeks
epidemiologist one day, and a biologist the next day, and to give undergraduates that opportunity, to give them the
a political scientist the next day…We learn about things chance to be able to work with professors and contribute
that are going on in other fields that we would never think to the “Eureka!” moment. “You should experience the
would relevant, but turn out to be.” This range of interests thrill of a discovery,” King says. “Every undergraduate
is also apparent in the composition of the Institute. “It’s should get that opportunity.”
a pretty diverse group of people that end up hanging

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understanding the functions of
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By Jung Soo Lee ’12, THURJ Staff
T hroughout the bodies of most animals, specialized

cells called neurons form intricate networks that
serve as highways for information transmission and
Although C. elegans is a popular model organism, neu-
rological studies of the roundworm have proven to be
rather challenging – its neurons are relatively small and
processing. These numerous junctions (also known as a tough cuticle covers the length of its entire body. As a
synapses) allow neurons to relay information through- result, only one neuron could be studied at a time, under-
out the entire body. Take the nematode Caenorhabditis mining previous efforts to study the activities of neural
elegans (C. elegans), for example. In the nervous system circuits. In late 2009, however, Zengcai Guo, Professor
of this miniscule roundworm of approximately one mil- Anne C. Hart of the Harvard Medical School, and Profes-
limeter in length, over 7000 synapses form connections sor Ramanathan of Harvard University published a find-
between only 302 neurons. ing in the journal Nature Methods that offers a glimpse
While previous studies have elucidated the details of into a technique that could revolutionize future studies
the physical connections among these neurons, little is of synaptic function. This new approach uses an optical
yet known about the functional nature of these synaptic method to excite specific neurons while simultaneously
links. However, scientists at the FAS Center for Systems measuring the activity of other subsets of neurons.
Biology and Harvard Medical School have recently been By combining various genetic techniques with an
able to devise a novel optical method that allows a deeper intricate system involving lasers and mirror arrays, these
examination of neural circuit function. researchers were able to observe the interactions among
Zengcai Guo, a researcher in the lab of Professor Sha- distinct groups of neurons. One neural system scientists
rad Ramanathan (an assistant professor of Molecular and examined using this method was composed of synaptic
Cellular Biology and Applied Physics) describes this new connections between ASH sensory neurons and AVA
approach as “a powerful new tool for analyzing small and AVD command interneurons. ASH neurons react to
neural circuits [that] allows scientists to directly measure various types of harmful mechanical and chemical stim-
how neurons talk to each other.” uli, causing the worm to initiate an avoidance response
While the physical map of the nervous system of C. through the AVA and AVD command interneurons,
elegans is well characterized, Guo relates that “To my which are required for backward movement. Previous
surprise, it’s still difficult to understand how the ner- studies had demonstrated that ASH neurons form synap-
vous system [regulates] animal behaviors even with the tic connections with the AVA and AVD command inter-
‘wiring diagram’ of C. elegans mapped out. One crucial neurons and that the activation of ASH neurons causes
piece of information missing is that we typically don’t the simultaneous activation of AVA and AVD command
know whether a synaptic connection between neurons interneurons.
is excitatory or inhibitory.” First, the researchers activated channelrhodopsin-2
www.thurj.org 137
(CHR2) expressing ASH sensory neurons. Originally both ChR2 and GCaMP. “GCaMP is a genetically encoded
found in green algae, ChR2 is an ion channel that can calcium indicator. Like fluorescent proteins, it does not
be activated by specific wavelengths of light. Upon acti- emit light [by itself],” says Guo. “However, GCaMP emits
vation of these channels in ASH neurons, the optical green light when exposed to blue light. ChR2 is an opsin
system allowed the scientists to simultaneously measure protein which functions as light sensitive channels. When
neuronal activity in AVA and AVD command interneu- exposed to blue light, ChR2 molecules undergo con-
rons through the detection of calcium activity by the formational changes and allow ions to flux into cells
expression of GCaMP, which increases fluorescence in expressing ChR2.” However, Guo explained, because both
the presence of calcium. ChR2 and GCaMP respond to blue light, their excitation
The simultaneous activation of specific neurons and spectra are not always distinct. Thus, researchers had to
measurement of activity in other groups of neurons devise a method to effectively separate neural activation
were accomplished through the use of a sophisticated using ChR2 and calcium activity measurement through
system of mirrors and light sources. In this process, the GCaMP. In order to do this, Ramanathan and colleagues
initial activation of ChR2 is executed by a light source opted to use a high-power light source to activate neu-
that hits a digital light processing mirror array. Each of rons and a lower-intensity laser to measure GCaMP
!
these miniature mirrors can fluorescence.
be precisely manipulated in The researchers were also
order to accurately orient ...this method will faced with the difficulty of
the light source on specific
locations on the C. elegans.
allow scientists to precisely activating only neu-
rons of interest, leading to the
Meanwhile, a system involv-
ing a laser, spinning disc,
understand exactly development of the mirror
array that permits the accu-
and camera would measure how those connections rate aiming of light at a specific
calcium activity in other group of neurons.
neurons through the detec- actually function in order The successful develop-
tion of GCaMP fluorescence. ment of this method is a major
The researchers first con- to relay information breakthrough that will allow
firmed that light activation scientists to better understand
of ASH sensory neurons results in the classic C. elegans how our neurons build connections and form networks.
avoidance response. Then they recorded GCaMP fluo- “The idea of combining light sensitive channels and
rescence levels in AVA and AVD command neurons, and genetically encoded calcium sensors to develop an all
successfully showed that the intensity of GCaMP fluo- optical method is quite general,” describes Guo. “We
rescence in these interneurons increased after activation expect this method can be widely used in C. elegans and
of the ASH neurons. zebrafish larvae (as it’s also transparent) to study small
The development of this method was not without chal- neural circuits. It might also be adapted to study local
lenges. One major setback was finding a way to overcome neural circuits in high reorder animals such as mice.”
the limitations of the overlapping excitation spectra of Even though the many synapses in C. elegans have previ-
ously been mapped, this method will allow scientists to
understand exactly how those connections actually func-
tion in order to relay information throughout the entire
organism to evoke certain behaviors and responses. These
types of research and methods will prove to be crucial
and invaluable as scientists strive to apply fundamental
findings at the molecular and cellular level to the greater

understanding of organism function as a whole.
Source:
Optical interrogation of neural circuits in Caenorhabditis
elegans. Zengcai V Guo, Anne C Hart, and Sharad Ram-
anathan. Nature Methods, December 2009, Vol. 6 No. 12
What underlies cancer:

A collaborative study unearths common
mutations
By Patrick Snodgrass ‘13, THURJ Staff
S ince their inception, the Broad Institute of Harvard

and MIT and the Dana Farber Cancer Program have
been interested in researching the genetic underpinnings
these copy number changes that result from cancer, he
asserts, has only been available in the last few years with
the development of the single nucleotide polymorphism
of cancer. As a result, it is no surprise that in 2004 these (SNP) array, which allows researchers to determine the
two institutions decided to collaborate with the Meyer- genetic code of a cancer sample at numerous polymorphic
son, Sellers, Getz, and Lander labs at Harvard Medical sites in the genome.
School (HMS) and MIT to fund the largest study in his- The Meyerson lab extended the use of the SNP array
tory investigating the mutations underlying cancer. when they applied it to SCNAs. As Mermel describes,
In this massive study, researchers have mapped and “What Matthew’s [Meyerson’s] lab was interested in early
statistically analyzed the somatic copy number altera- on was extending this technology to enable you to actu-
tions—common insertions and deletions of genetic ally read out the intensity of the DNA in addition to
!
material implicated in the genotype.” Researchers
cancer—of 3,131 can- could then determine how
cer specimens from a ...the researchers many copies of a particular
range of cancer types. gene were present in a cancer
The data unearthed from have made the startling sample based on how much
this research has enabled
the researchers to iden- discovery that the majority DNA was interacting with
the SNP array probes. This
tify numerous previously
undiscovered oncogenes.
of mutations that lead allowed the lab to document
the copy number of approxi-
In addition, researchers to cancer are conserved mately 250,000 genes in each
have made the startling cancer sample.
discovery that the major- among all cancer types. In order to determine the
ity of mutations that lead significance of the informa-
to cancer are conserved across all cancer types. The data tion gathered from this study, the researchers still had to
amassed has yielded a wealth of information about the develop a set of statistical tools to analyze the massive data
mutations shared among all types of cancer. In the pro- sets they gathered. Dr. Rameen Beroukhim, an associate
cess, the study has revealed exciting new research avenues professor at HMS, provides insight into these statistical
in the fight against cancer, resulting in a seminal Nature tools. He explains that “the way we determine which copy
publication and numerous new opportunities for future number changes are important is we determine which
work. ones rise above the background rate” of mutations that
would normally occur without the presence of cancer. The
Step 1: The Technology collaboration between his lab and the Meyerson lab over
the last two to three years has resulted in the development
Craig Mermel, a graduate student in Matthew Mey- of this methodology.
erson’s lab, was heavily involved in this research study. Relying on both of these technologies, the research
Describing somatic copy number alterations (SCNAs), collaborative analyzed 3,131 cancer samples for copy
Mermel explains, “[cells] gain some regions of the number alterations at approximately 250,000 sites with
genome and lose some regions of the genome” when they an SNP array. They then used newly developed statistical
are altered by cancer. The technology necessary to map tools to determine which genes had statistically significant
www.thurj.org 139
Step 3: The Implications

copy number alterations across its cancer type and across
all cancer types. This analysis gave them the data they In the process of analyzing these data sets, these
needed to make the following salient conclusions. researchers identified many genes such as those regulated
by NF-κB as well as the genes MCL1, BCL2, and BCL2L1,
Step 2: The Results which are most conserved among cancer types. Many of
these genes were not previously believed to play a large
After amassing sizeable datasets and statistically ana- role in cancer. Since cancer therapy is increasingly mov-
lyzing these datasets within and between cancer types, the ing towards addressing the underlying biology of cancer
research group was able to come to two major conclusions. after the success of Gleevec in treating chronic myeloid
First, the two different types of SCNAs (arm-level and leukemia, these genes provide new targets for researchers
focal) differ in their correlation to developmental lineage. designing new cancer therapies.
Arm-level SCNAs occur when chromosome-length pieces This study also addresses a large debate within the
!
of the genome are gained cancer research com-
or lost, and focal SCNAs munity as to whether
occur when very short This discovery goes against cancer should be
pieces of the genome are treated as one or a
gained or lost. Whereas the current movement in the handful of diseases
the same arm-length
SCNAs appeared in can- cancer research community with numerous man-
ifestations or as a col-
cers that arose from the
same developmental
of focusing on cancer as lection of thousands
of different diseases
lineages, focal SCNAs thousands of separate diseases. each with its inde-
showed differing pat- pendent mutation
terns. The data from only arm-length SCNAs, Mermel signature. Although Beroukhim believes that “there will
says, demonstrated that “whatever pattern of changes continue to be important effort in both directions,” the
that you get seems to be constrained by some larger study does provide evidence that it is possible to look
developmental lineage. There is some organization to for cancer therapies that address the conserved genetic
cancer.” However, some other force seems to be driving underpinnings of all cancer types. This discovery goes
the changes in focal SCNAs. against the current movement in the cancer research
Second, although cancer researchers have known for community of focusing on cancer as thousands of sepa-
a long time that certain mutations are common among rate diseases.
all cancers, in the case of SCNAs, this group was able to Finally, the study provides insight into a new way to
quantify to what extent all mutations caused by cancer diagnose cancer. “We are still diagnosing lung cancer
were conserved among all cancer types. As Beroukhim by looking at it under a microscope,” says Mermel. He
states, “we started to find that the events that were recur- goes on to state that this study shows that it would be
rent in any one cancer type tended to also be recurrent in much more effective to diagnose cancer not only by tissue
other cancer types.” What is most surprising, as Mermel type but also by the mutations that lead to that cancer.
asserts, is that “eighty percent of the lesions in one cancer Although it would take time to develop the technology
type are present in other types.” and therapies necessary to make this a reality, it would
lead to much better treatment outcomes.
Illustration By Sam Mendez

Step 4: Future Work

As a result, Beroukhim asserts that it is integral to extend
Despite the success of the study, there is much work this study to identify “point mutations and other sources
that must be done to extend and verify the results. of genetic changes like translocations and fusion events.”
Although over 3,000 cancer specimens were analyzed, What these researchers are eventually working toward is a
the researchers understand that many conserved genes study that analyzes all types of mutations across hundreds
were missed. As a result, Mermel says, “we’d love more of samples from every cancer subtype. The hope is that
samples.” The more samples they analyze, the more small such a study will enable doctors to design more effective
SCNA events that can be identified. Thus, this is one diagnostic and treatment options for cancer. However,
major area of research that both Mermel and Beroukhim such a study is years away from realization.
are currently investigating. This massive study was made possible only through the
Using a higher resolution SNP array would also allow partnership of multiple labs at both Harvard and MIT as
these researchers to identify more conserved mutations well as through the support of numerous organizations
as well as glean more accurate information about the such as the Dana Farber Cancer Institute and the Broad
extent of their conservation. Regarding the current state Institute. As the natural sciences, and especially the bio-
of SNP array technology, Mermel comments, “where we medical sciences, become increasingly interdisciplinary,
had 250,000 markers across the genome, we can now do such seminal work is often only possible through these
this at 2,000,000 markers across the genome.” Mermel academic and research partnerships. From the enthu-
even goes on to state that it is now possible to sequence siasm for scientific collaboration and partnership that
the entire genome of these cancer samples, which would pervades the Beroukhim and Meyerson labs, the chal-
enable perfect resolution. Analyzing cancer samples at lenges that these researchers will face as they extend this
higher resolution is thus another area of interest. study and probe its implications will surely be confronted
Finally, this study only looked at SCNAs, which are but through the collaborative spirit that has driven their suc-
one of numerous types of mutations involved in cancer. cess to date.
www.thurj.org 141
BOOK REVIEW Volume 3 Issue 2 | Fall 2010
!!!!!!!!!!"#$"%!&'!())
*!+,-.,/!01!*234!56/678,9:!;62,:2!<00=!
By Alissa D’Gama ‘11, THURJ Staff
I n The Checklist Manifesto, Atul Gawande, the author

of Better and Complications and a general and endo-
crine surgeon at Brigham and Women’s Hospital, spends
they know how their patients are doing, Gawande notes
that doctors, with their year of training and “superspe-
cialization” don’t think they need them. The checklists
193 pages talking about an idea that seems ridiculously seem silly, even stupid.
simple: the checklist. In other areas of specialization; however, checklists
Whether the reader is an aviation pilot who has used have become the norm, a requirement for the profession.
hundreds of checklists during takeoff and landing (an Gawande describes his visit to a construction site, where
example Gawande refers to frequently throughout the large sheets of paper contained detailed checklists for
book), a college student who would be lost without the tasks to be completed and the order in which they
Google Tasks, or a cubicle worker whose board is tacked should be completed, the people who needed to talk and
with scribbled post-it notes, the book gets across its point. whether that communication had taken place. When he
Using a checklist may seem silly, but as the reader can sits in the kitchen of renowned Boston chef Jody Adams,
attest from the mundane experience of crossing items off owner of Rialto, he sees a similar checklist in place—the
a grocery list and as Gawande demonstrates through a recipe, with modifications and the chef ’s notes—which
World Health Organization study, the checklist can catch every cook had to follow to prepare the food for each
common mistakes and, in surgery, save lives. customer, all of whom had their own checklist to make
In the introduction, Gawande asks why we fail at what sure their meal was delivered to their satisfaction.
we do. Either we do not know the answer, he surmises; As the reader goes along with Gawande, savoring
or, we know the answer but fail to apply the knowledge Adams’s grilled clams and admiring the towering sky-
correctly—a growing problem in our world today, with scraper built from a series of checks, we begin to wonder
the explosion of information and lack of organization. what Gawande has thought all along—can this simple
Yet, in a field such as surgery, where the unexpected is checklist be used effectively in surgery?
the norm and where many deaths are avoidable, hospitals At a World Health Organization meeting in Geneva
must find a way to help the entire team—the surgeon, in 2007, Gawande recalls
the resident, the anesthesiologist, the scrub nurse—apply how Dr. John Snow
their knowledge in a situation of life and death. A simple traced a cholera out-
checklist, Gawande argues, could make this difference. break in London in 1854
Surgeons lead busy lives, often performing multiple to a public well. By map-
procedures in a day on little sleep and sharing an operat- ping where those who
ing room with a team they may not know. In this complex died had lived he found
environment, it is easy to forget things that are important them surrounding a
and it is easy to purposely forget things that are impor- single water source,
tant but that a surgeon knows from years of experience and, upon convincing
don’t always matter. Unfortunately, these mistakes can the local government
be costly. Gawande describes how the recording of vital to remove the water
signs—blood pressure, pulse, temperature, and medica- pump handle, the dis-
tion—didn’t become routine until the 1960s. Yet while ease ceased to spread.
nurses have put these checklists in place, making sure The contaminated water
Volume 3 Issue 2 | Fall 2010 BOOK REVIEW
had been the culprit, and a simple intervention—remov- thing was real,” the reaction of surgeons was still mixed.
ing the pump handle—had been the cure. Gawande real- Yet, he tellingly reports that when staff members who
izes the intervention for surgery needs to similarly be used the checklist in surgery were asked “If you were
“simple, measurable, [and] transmissible.” The checklist having an operation, would you want the checklist to be
seemed ideal. used?...A full 93% said yes.”
There are four main killers in surgery, Gawande Gawande acknowledges that the checklist has not
explains: infection, bleeding, unsafe anesthesia, and the caught on everywhere, and not only in medicine. “We
unexpected. Clearly, the last is the hardest to prepare don’t like checklists,” Gawande says. “They can be
for. A checklist can prevent the first three, but address- painstaking. They’re not much fun…It somehow feels
ing the fourth is complex—and beneath us to use a checklist, an
so the checklist included a step embarrassment.”
requiring the surgical team to But much like the checklists
introduce themselves and talk pilots use every day to ensure
about the surgery, so that, as the plane is ready for takeoff, the
!
much as possible, they could checklists Gawande and his team
anticipate the unexpected. A designed for surgery “gets the dumb
WHO team condensed avail- The checklists stuff out of the way, the routines
able checklists into one master your brain shouldn’t have to occupy
checklist—nineteen steps, with have made a itself with…and lets it rise above to
three pause points: before giv-
ing the patient anesthesia, before difference. Perhaps focus on the hard stuff.”
In The Checklist Manifesto, Gawa-
making the first incision, and
before wheeling the patient out
their greatest asset nde presents a compelling argu-
ment, drawing the reader into his
of the operating room. Then the is that they make us world as a surgeon and into the
checklist was put to use in eight daily lives of contractors, pilots, and
hospitals around the world to pause for a minute in even chefs, all of whom have used
see if it worked. the simple checklist and achieved
Gawande admits he was our rushed lives and awing results. Surgery, anyone will
nervous about the study. What
if the checklist had no effect? think about what we admit, is risky and dangerous. “No
matter how routine an operation is,
Then the surgeons who scoffed
at it would be right. So when
are actually doing. the patients never seem to be. But
with the checklist in place, we have
his research fellows excitedly brought him the results, caught unrecognized drug allergies, equipment problems,
Gawande, instead of “dancing a jig on my desk”, poured confusion about medications…We’ve made better plans
over the papers for errors. But the results held—as Gawa- and have been better prepared for patients.” The check-
nde writes, “the rates of major complications for surgical lists have made a difference. Perhaps their greatest asset
patients in all eight hospitals fell by 36% after introduc- is that they make us pause for a minute in our rushed
tion of the checklist. Deaths fell 47% percent…Infections lives and think about what we are actually doing. In that
fell by almost half...Overall, in this group of nearly 4,000 regard, all of us could use a checklist, whether or not we
patients…Using the checklist had spared more than 150 are about to perform a complex operation on a patient
people from harm—and 27 of them from death.” who has entrusted their life in our hands.
And although Gawande triumphantly writes, “This
www.thurj.org 143
OP-ED Volume 3 Issue 2 | Fall 2010
!"#$%&"'()%*+,%
may seem odd in an era where Intel commercials joke that
their employees are akin to rock stars and when a forth-
coming movie about Facebook, a site created in a Harvard
-#%*,+.)%*+,%
dorm room, has immense cultural currency. Shows like
Lost and Fringe openly discuss quantum physics, nuclear
power, and time travel. And Iron Man’s “superpowers”
are very much of this earth.
!"#$$%&'(&)*$$+%,&-#+.&/0&1"#&2+$3 Of course, engineers design, build, operate, and repair
4+$5& 67"//8& /0& 9.:;.##$;.:& +.5& things—often incredibly cool things like iPads and robotic
'<<8;#5&67;#.7#=>&?/".&'(&+.5&98;@+3 flies and, well, oil rigs. But more often than not, they try
A#1"&6(&'$B=1$/.:&C$/0#==/$&/0&9.:;3 to figure out how entire systems work (or don’t work) and
.##$;.:&+.5&'<<8;#5&67;#.7#=>&+.5& how technology interfaces with everyday life.
C$/0#==/$&/0&C"%=;7= Engineers have a knack for learning valuable lessons
from failure. My predecessor, Dean Venky, liked to say
When the President of the that engineering was first and foremost a way of thinking.
United States calls, you answer. About anything. I completely agree.
In June I was appointed to the Take another kind of oil. At the kickoff of the Sci-
National Commission on the BP ence and Cooking public lecture series, affiliated with the
Deepwater Horizon Oil Spill and Offshore Drilling. In astoundingly popular new Gen Ed course, chef Ferran
fact, as I write this, I am just back from New Orleans, Adrià made encapsulated olive oil—little yellow beads
where I boarded a helicopter to visit the sister rig to the that look like caviar.
one that was destroyed. The twelve-acre structure, about He mentioned other culinary breakthroughs. Creating
the size of a Navy Destroyer, is located an hour-and-a-half hot jellies. Producing raviolis with skin made from the
away from the nearest heliport. same substance as the sauce. While all were showstop-
All of us on the commission have been asked about pers, his real love, he said, was the process, or completely
!
our role and ultimate rethinking the language, and
aim. Keeping in mind increasingly, physics of food
that I cannot reveal any- My predecessor, Dean Venky, and cooking.
thing specific prior to the
report, I can say that we
liked to say that engineering Adrià held up a glass of
water to demonstrate. Looking
are not looking to design was first and foremost a way at it intently, he began to break
and build a better oil rig it down as an experimentalist
or to assess the nature of
of thinking. About anything. I would, asking about its char-
drilling per se. Instead, we completely agree. acteristics, properties, color,
are charged with examin- and texture. He uses this same
ing the facts and circumstances behind the root causes of technique for all of his fantastic dishes, but he went one
the disaster and developing options for guarding against step further. You could, of course, treat water as an ani-
and mitigating the impact of future oil spills caused by mal does, he said, as a basic means to quench thirst. Then
deepwater drilling. again, he added, as his eyes lit up, you could see the water
That may, then, sound like work just for politicians and as an immensely complicated system, related to bigger
policy makers. Engineering, however, is at the heart of the issues like the environment and economics.
process. The Commission needs to solve a mystery: rec- Adrià, who said he is a mere cook (ha!), must also be
reating, with incomplete data, how and why the blowout an engineer at heart. The same kind of engineer that we
and explosion that sank the rig occurred—when those are training at Harvard: those grounded in the liberal arts,
who know the most about the minutes and moments deep in a technical subject, but able to stretch across to
leading up to the tragedy are no longer with us. other areas. The kind of person who looks at something
It is, in short, working under massive constraints, or as simple and clear like water and sees an entire universe
doing exactly what engineers are trained to do. of possibilities.
The image of engineers and engineering is more accu- Because one day, our students are going to get a similar
rate than it once was, but still needs some updating. That call to my own—and we want them to be ready.
įĽľňľňňŊĺńĻįģİĭĥŌĶňłĶĹĺŅńňňľķŁĺķŎ
ļĺŃĺŇńŊňňŊŅŅńŇŉĻŇńł
ĲľŉĽŅĶŇŉľĸŊŁĶŇŉĽĶŃŀňŉńġĜĮğĺĶŃńĻĮĸľĺŃĸĺĥĺŇĺłŎĝŁńōĽĶłğĺĶŃ
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Gerstner Sloan-Kettering
Graduate School of Biomedical Sciences
The Gerstner Sloan-Kettering Graduate School of Biomedical

Sciences offers the next generation of basic scientists a program
to study the biological sciences through the lens of cancer —
while giving students the tools they will need to put them in
the vanguard of research that can be applied in any area of
human disease.
An Internationally Recognized Research Faculty in:

s #ANCER GENETICS s )MAGING AND RADIATION SCIENCES
s #OMPUTATIONAL BIOLOGY s )MMUNOLOGY
s 'ENOMIC INTEGRITY s /NCOLOGY
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s #ELL SIGNALING AND REGULATION s 'ENOMICS
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ǯǯȱȱȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱȱȱǯȱřȱ ȱŘȱȱȱȱȱŘŖŗŖ

Dear Harvard Community,

Undergraduate Research Advisor in Life Sciences

The Harvard Undergraduate Research Journal

Dear Harvard Community,

John Mei Grace Cho

75 Surface morphology and electrical properties

123 Development of an automated head-fixed

142 Check it off: A review of Atul Gawande’s

144 From crude oil to olive oil

Managing Editor of Content Executive Board

Boards Faculty Advisory Board

Copy Editors: Caroline Huang ‘13 Julie Chang ‘14

About the Cover

Photo credit: Melissa Deas

Who Has the Right to Define Place: Authenticity

72 The Harvard Undergraduate Research Journal

of Compounds 3.0 and 3.3 that are important in their function as

Whether it’s smart, flavored, or vitamin-enriched, water always References:

of Ayn al-Basha, Jordan. In this area, the government has a monopoly

Development of an automated head-fixed

Photo by Kate Xie

74 The Harvard Undergraduate Research Journal

Surface morphology and electrical

University of California, Santa Barbara, Materials Department

Introduction dislocation densities in heteroepitaxial film growth, as well as to

Figure 1. (left) Structure of AlGaN/GaN showing

Figure 2. (right) GaN growth diagram: blue

!"#$%&'(345 65 748 !"#$%&'(345 65 748

Surface morphology analysis Results

/-.&.. 4567"389:;:<! 0..

Figure 5 (top), Figure 6 (bottom) Figure 7 (top), Figure 8 (bottom)

composition and AlGaN thickness was found at which Hall mobil-

Sheet Carrier Density and Hall Mobility

80 The Harvard Undergraduate Research Journal

Discussion ratios. This was reflected by differences in electron mobility within

Who has the right to define place:

Harvard University, Department of Sociology

Table 1. Median Household Income ($) by Census Tract in HJS adjusted

Moreover, in Zukin’s opinion, the presence of gentrifiers in these

Structure-function analysis of newly-

Harvard Medical School

this low pH is required for the endosomal cathepsin L (CatL) and

Figure 3. (3a) Structure of Compound 3.0 includes four arbitrarily assigned

form the substituted benzylpiperazine 3.3 derivatives was unsuc-

Based on Katritzky et al.’s work, I proposed the following reaction

scheme to synthesize the substituted benzylpiperazine Compound

Table 1. Synthesized 3.0 derivatives with variations in methylene linker

Anti-Ebola activity of Compound 3.0 derivatives

GFP virus assay

AA6 543.7 55 ± 6 Methylene linker

Amino acid linker

AA9 448.6 28 ± 7 Benzylpiperazine

B11 453.6 79 ± 11 B27 410.6 25 ± 5

Cl Anti-Lassa activity of 3.3 derivatives

Electron-withdrawing substitutions and

GFP virus assay

glycine amino acid linker, and an unsubstituted benzylpiperazine

Compounds could be blocking cell targets

then para substitutions. Fused rings are not

100 The Harvard Undergraduate Research Journal

Conclusion 3.0 (Figure 6). Compound 3.47 incorporates many conclusions I

mechanism might help to elucidate analogous processes.

11. Wool-Lewis RJ, Bates P. Characterization of Ebola virus entry by using

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!"#$!%!&'()&)'+!),-%!%)./'-'&'&0)#1)'+!)#2!3&4!%'&1(&%$)3!*'3&0'&#%) may affect the quantity of tanker water demanded if a household

of (T, F). We have |R| = |V(D)| - size(T, F) = |V(D)| - size(T, F*) =