The Tower Undergraduate Research Journal Volume VI, Issue I

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The Georgia Tech Research Institute
(GTRI) is a highly regarded applied research
and development organization. Founded
in 1934, GTRI is an integral part of the
Georgia Institute of Technology, one of the
worlds top-ranked research universities.
With more than 1,500 scientists, engineers
and other professionals, GTRI helps
solve the most difcult problems facing
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www.gtri.gatech.edu
Want to break from the crowd?
theres a lab for that.
WWW.GTRI.GATECH.EDU/CAREERS/STUDENTS
JOBS FOR STUDENTS

The Georgia Tech Research Institute
(GTRI) is a highly regarded applied research
and development organization. Founded
in 1934, GTRI is an integral part of the
Georgia Institute of Technology, one of the
worlds top-ranked research universities.
With more than 1,500 scientists, engineers
and other professionals, GTRI helps
solve the most difcult problems facing
government and industry across the nation
and around the globe.

www.gtri.gatech.edu
WELCOME LETTER
GEORGIA INSTITUTE OF TECHNOLOGY
OFFICE OF THE PROVOST
225 North Avenue
Atlanta, GA 30332-0325
Tel: 404.385.2700
Fax: 404.894.1277
January 2014
Dear Reader,
A vital part of research and scholarship is educating others on the work we do and why it maters. That is
why it is gratifying to see each of this issues contributors a new generation of students starting to test their
own ideas engaged in this brave, public act in the pursuit of scientifc insight and discovery.
Why brave? In forming my own career as an engineer and scientist, I understood the value of opening my
research fndings to the scrutiny of peers and colleagues. This is not a painless process, I assure you. Yet if you
can tame the healthy fear of public criticism, you will be beter for it. The public review process is incredibly
instructive, instilling discipline, building character, and sometimes taking you in entirely new directions.
At Georgia Tech, our mission is to defne the technological research university of the 21
st
Century. The word
defne is very important. We are not waiting for others to pave the way for us. We want to lead the way by
exploring the vast possibilities, seting our own agenda, and sharing our goals and successes with the world.
For our contributors, publishing results in The Tower represents a frst step forging their own path into
a larger world. Not all will go on to a life of research, but the experience is what maters. Asking your own
questions, seeking answers through experimentation, contributing to the intellectual archive, and defending
your conclusions: these are the critical behaviors of experiential learning.
If we are to be among the most highly respected learning institutions in the world, Georgia Tech must ensure
its students are prepared to evaluate, analyze, and resolve the stubborn problems of society. The articles in
this issue of The Tower are evidence that Georgia Tech has achieved that goal and that our students can do
that. Congratulations!
Regards,
Rafael L. Bras
Provost and Executive Vice President for Academic Afairs
Georgia Institute of Technology
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4 | The Tower | Volume VI, Issue I
It is with great excitement and honor that
I present to you the sixth volume of The Tower
Undergraduate Research Journal! Over the past
three years that I have been with The Tower, the
journal has evolved into a national venue to
showcase Georgia Tech undergraduate research.
In the past several months as Editor-in-Chief, my
staf and I have created publishing collaborations
with peer institutions such as MIT, increased the
frequency of our open-access electronic publish-
ing, and developed a mobile application to freely
share the journals content. The Tower also has a
new home, as it has been selected to reside within
the collection of the United States Library of Con-
gress.
It has been incredibly rewarding to witness
and lead this growth, which has prompted me to
hasten and refect. As a biomedical engineering
student, I consider William Harveys discovery
of a systemic circulatory system one of the most
elegant scientifc achievementsnot just because
of the fnding itself, but because he fundamental-
ly changed conventional scientifc thought. Har-
vey, perplexed by Galens teaching of two sepa-
rate circulatory systems, had dissected all types
of vertebrates, with a focus on the bloods pre-
cise course through the veins, arteries, heart and
lungs. Harvey had proved Galen wrong by build-
ing of the work of Padua, Versalius and Fabricus.
It is rare even today that we completely discount
previous reports in the literature with one earth
shatering discovery. Rather, experiments are
built upon the works of others, each contribut-
ing pieces of data that lead us to the pathway of
truthor at least todays truth. The purpose of a
scientifc journal is to bring forth new ideas and
new techniques, to illuminate colleagues about
the unknown and to foster discussion and con-
troversy. As researchers, we should all be grasp-
ing for a beter understanding of the questions
that remain and the answers unatained.
In this issue of The Tower, we feature a paper
on one of the most controversial pieces of legisla-
tion of the 21st century: the Patient Protection and
Afordable Care Act. From our partners at the
MIT Undergraduate Research Journal (MURJ),
we host an article on the synthesis of biopoly-
mers for applications in cell and tissue engineer-
ing. The depth and breadth of undergraduate re-
search at Georgia Tech is fully refected in all the
works prepared within this issue.
The Tower could not be possible without
the tireless work of the Editorial Boardand
as such, they deserve special recognition. Chris
Harper, Ravi Konjeti, Amrita Banerjee and Jes-
sica Block are the warriors of the Review Team,
each equipped with formidable expertise and pa-
tience. Andrea Hu and Katie Staples never cease
to impress with their creative skills and produc-
tion of the journal. Reeves Broussard is a gifted
leader running the Business Team. And fnally,
Harsimran Mann is an energetic driver of inspi-
ration, who will truly be missed as he starts his
career at SpaceX this spring.
Each volume refects the dedication and sup-
port of several individuals. I want to personally
thank all student and faculty reviewers, graphic
designers and developers for their roles. As well, I
am incredibly indebted for the support and men-
torship of Dr. Carole Moore, Dr. Karen Head, Dr.
Chris Reaves, Dr. Rafael Bras, Mr. Mac Pits, Mr.
Tyler Kaplan, and Mr. Michael Chen. Of course,
we are driven everyday by your readership and
loyalty. Thus, I am excited to share with you the
sixth volume of The Tower. I am hopeful you will
fnd inspiration in its pages.
Sincerely,
Mohamad Ali Najia
Editor-in-Chief, The Tower
WELCOME LETTER
The nat i onal s t age awai t s
Mohamad Ali Najia
Editor-in-Chief
Correspondence:
Ofce of Student Media
353 Ferst Drive, Suite 137
Email:
editor@gtower.org
GTTOWER.ORG | 5
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13
NEWS
Undergraduate research journals patern to foster
undergraduate research
Amrita Banerjee
14
16
17
TABLE OF CONTENTS
VOLUME VI, ISSUE I
Spring 2014
Vertically-Integrated Projects support student
innovation
Jessica Block
The mathematics of criminal behavior
Christopher Harper
It all maters: The discovery of the Higgs boson
Ravi Konjeti
19
I NTERVI EWS
SPOTLIGHT: Previous Authors in The Tower
20 SPOTLIGHT: Keith McGreggor, Director of the Georgia
Tech VentureLab
BI OLOGY
Involvement of RNase H enzymes in ribonucleotide
extraction and Aicardi-Goutires Syndrome
Lahari Shety & Francesca Storici, PhD
26
PERSPECTI VES
BI OMEDI CAL ENGI NEERI NG
Implications of highly active antiretroviral therapy
in the development of cardiovascular disease in HIV
patients
LaDeidra Monet Roberts & Manu Plat, PhD
29
PUBLI C POLI CY
Open access for our generation
Joseph Elsherbini
22
About t he Cover
The Tower features Vivian C. Lacayo and Dr.
Kari Davis-Nozemacks paper on the Aford-
able Care Act and small businesses in Amer-
ica. Designed by Katie Staples, the cover
portrays a stethoscope in the foreground
symbolic of the new healthcare lawand the
American fag in the background, symbolic of
American ideals, of which entrepreneurial
spirit and business ownership is core. Their
paper is positioned in the middle-ground to
mediate potential solutions to the challenges
the healthcare law poses in relation to small
businesses.
29 | 3D rendering of cathepsin L
AutoTrader Group operates the worlds largest digital automotive marketplace
and provides marketing and software solutions to automotive dealers
throughout the U.S. As leaders in our space, our companies have
transformed the retail automotive industry. With outstanding
opportunities in Technology, Business Operations, Marketing and
Sales, at AutoTrader Group your career path is yours to invent.
Were changing the way
people buy and sell cars.
Want to help?
To learn more visit
Careers.AutoTrader.com
GTTOWER.ORG | 7
TABLE OF CONTENTS
56
ARTI CLES
I NTERNATI ONAL AFFAI RS
Immigration trends and atitudes: Is the United
Kingdom an anomaly?
Shannon Kehoe & Vicki Birchfeld, PhD
64 SOCI AL SCI ENCES
Child and marriage culture, womens infuence outside
the home, sex and STI education, and homosexual
rights
Robey-Phillips, Heisler, Wall, Brown & Brecke
46
ELECTRI CAL ENGI NEERI NG
Improved signal integrity and power consumption in
high speed digital circuits
Sinan Liu & Madhavan Swaminathan, PhD
76
LEGAL STUDI ES
FEATURE ARTICLE: The efects of the Patient Protection
and Afordable Care Act on small and medium-sized
American businesses
Vivian C. Lacayo & Karie Davis-Nozemack, PhD
82 CHEMI CAL ENGI NEERI NG
THE TOWER-MURJ FEATURE ARTICLE: Synthesis of
polypeptides for hydrogel scafolds
Kiara Cui, Mackenzie Martin & Paula T. Hammond, PhD
35
Delineation of cell-based therapies to treat insulin-
dependent diabetes
Thuy Le & Athanassios Sambanis, PhD
32
Chronically elevating bursting results in distinct
homeostatic changes of cultured neuronal network
activity
Rachel Candace Law & Steve Poter, PhD
40
DI SPATCH
Robotic exoskeletons and the challenges facing the feld
Harrison Bartlet & Lena H. Ting, PhD
35 | Robotic exoskeleton
76 | High speed digital circuit board
40 | Visualization of neural networks
GTTOWER.ORG | 9
EDITORIAL BOARD
Editor-in-Chief
Mohamad Ali Najia
Managing Editor of Submissions & Review
Harsimran Mann
Managing Editor of Production
Katie Staples
Business Manager
Reeves Broussard
Section Editors
Amrita Banerjee
Jessica Block
Christopher Harper
Ravi Konjeti
Layout Editor
Andrea Hu
Webmaster
Richard Li
REVIEW STAFF
Undergraduate Reviewers
Christopher Andrew Arencibia
Casey Aultman
Kevin Dafon
Jaheda Khanam
Laura Lanier
Matias Leguizamon
Ang Li
Dionne McKenzie
Michael Merritt
Shamus Moran
Simisola Oludare
Christopher Pace
Hifza Sakhi
Apoorv Saraogee
Kunal Shah
Seung Ho Shin
Samantha Stadmiller
Hoki Tse
Sarthak Vaish
Graduate Reviewers
Shereka Banton
Amulya Chirala
Nikhilesh Natraj
Chris Quinto
Shriradha Sengupta
David Sotto
Jenna Wilson
Post-doctoral Fellow Reviewer
Pritha Bagchi, PhD
Research Scientist Reviewer
Gaurangkumar Patel, PhD
Faculty Reviewers
Tibor Beseds, PhD
Wayne Book, PhD
Amy DUnger, PhD
Monica Halka, PhD
Melissa Kemp, PhD
Narayanan Komerath, PhD
Don Lim, PhD
Lakshmi Sankar, PhD
FACULTY ADVISORY BOARD
Rosa I. Arriaga, PhD
Jefrey A Davis, PhD
Amy DUnger, PhD
Monica Halka, PhD
Marlit Hayslett
Pete J. Ludovice, PhD
Milena Mihail, PhD
Lakshmi Sankar, PhD
Han Zhang, PhD
ACKNOWLEDGEMENTS
Karen Adams, PhD
Charlie Bennett
Jon Bodnar
Ronald A. Bohlander, PhD
Rafael Bras, PhD
Beth Bryant
Rebecca Burnett, PhD
Michael Chen
Stephen Cross, PhD
Kirk Englehardt
Steven Girardot, PhD
Marlit Hayslett
Van Jensen
Tyler J. Kaplan
Kenneth Knoespel, PhD
Pete Ludovice, PhD
Carly R. Macdonald
Kathryn Meehan, PhD
Carole Moore, PhD
Catherine Murray-Rust
Thomas Orlando, PhD
Susan Parham
Donald Mac Pitts
Fred Rascoe
Christopher Reaves, PhD
Paulette A. Richards, PhD
Malavika Shetty, PhD
John Toon
Michael H. Yan
Lisa Yaszak, PhD
Han Zhang, PhD
SUPPORTING ORGANIZATIONS
Auxiliary Services
Board of Student Publications
Library Information Center
Undergraduate Research Opportunities
Program
Student Government Association
THE TOWER STAFF
Focus and Scope
The Tower is an open-access, interdisciplinary, peer-
reviewed research journal for undergraduate stu-
dents of the Georgia Institute of Technology. The
goals of our publication are to showcase undergrad-
uate achievements in research, inspire academic
inquiry, and promote Georgia Techs commitment
to undergraduate research endeavors. The Tower
publishes articles that may discuss theoretical or
empirical work, including, for example, experimen-
tal, historical, ethnographic, case study, and/or liter-
ary/cultural inquiry. The Tower strives to appeal to
readers in academia and industry. Articles should be
easily understood by bachelors-educated individu-
als of any discipline. Although The Tower will review
submissions of highly technical research for poten-
tial inclusion, submissions must be written to edu-
cate the audience rather than simply report results
to an expert audience in a particular feld. Submis-
sions of original research must be well supported by
evidence, arguments must be clear, and conclusions
must be logical. Fiction, poetry, and creative writing
will not be accepted.
Manuscript Types
The Tower welcomes manuscript submissions under
the following categories:
Article: manuscript that represents the culmina-
tion point of an undergraduate research proj-
ect, where the author addresses a clearly de-
fned research problem from one, or sometimes
multiple approaches
Dispatch: manuscript in which the author re-
ports recent progress on a research challenge
that is relatively narrow in scope, but critical to-
ward his or her overall research aim
Perspective: manuscript that refects active
scholarly thinking in which the author provides
personal viewpoints and invites further discus-
sions on a topic of interest through literature
synthesis and/or logical analysis
Synopsis: manuscript that provides a detailed
overview of an article already published in a
professional, refereed journal (of which the au-
thor must be a co-author), specifcally highlight-
ing the research the author was responsible for
Submitting to The Tower
Submissions to The Tower are accepted on a roll-
ing basis throughout the year. However, in order to
be considered for the upcoming issue, submissions
must be received by the announced deadline (see
gttower.org). Submissions are handled through our
Online Journal System (OJS). Please visit gttower.
org/submit for more information on submission
policies and access to OJS.
Copyright Information
The Tower is published as an open access publica-
tion and may be distributed in any format, including
on the Internet. The journal will be preserved and
made publicly available through the Georgia Insti-
tute of Technologys institutional repository, SMART-
ech (http://smartech.gatech.edu) and other open-
access repositories. Authors retain the copyright
ownership of the material and grant The Tower and
the Georgia Institute of Technology frst publication
rights and a non-exclusive license to distribute and
preserve this material for non-commercial, educa-
tional purposes.
Advertising in The Tower
The Tower is a great way to expose your business
to thousands of the countrys brightest engineers,
scientists, and students. Ad space is available for
purchase in the print version of The Tower. Approxi-
mately 3500 copies are printed each semester and
are distributed freely on the campus of the Georgia
Institute of Technology and to partner institutions
around the United States. For formatting informa-
tion and quotes, please contact business@gttower.
org.
Support
The Tower receives annual fnancial support from
the Georgia Tech Student Government Association.
The Tower is overseen by the Georgia Tech Board
of Student Publications and works in collaboration
with the Georgia Tech Library Information Center
and the Undergraduate Research Opportunities
Program.
Staf Positions
We are constantly looking for talented students to
join our team. To learn more about available posi-
tions and to fll out an application, please visit gt-
tower.org.
PUBLICATION INFORMATION
The Tower
Undergraduate Research
Journal
ISSN: 2330-0787
Editorial Ofce:
Ofce of Student Media
Georgia Institute of
Technology
353 Ferst Drive, Suite 137
Contact Information:
General inquiries and the
Editor-in-Chief:
editor@gttower.org
Faculty Advisor:
advisor@gttower.org
Business Manager:
business@gttower.org
Submissions & Review:
review@gttower.org
Production Team:
production@gttower.org
Webmaster:
webmaster@gttower.org
Website:
www.gttower.org
GTTOWER.ORG | 11
The Tower-MURJ
Article Exchange Program
The Tower Undergraduate Research Journal and the MIT Undergraduate Re-
search Journal (MURJ) have initiated a publishing collaboration to exchange
undergraduate articles to foster continued commitment to undergraduate re-
search endeavors and collaborations between Georgia Tech and MIT. Below we
highlight the Georgia Tech authors selected in this semesters exchange.
Helen is a third-year Electrical
Engineering major at Georgia
Tech. She is currently working
with Dr. Paul Kohl in the Inter-
connect and Packaging Center
research lab. She is the frst au-
thor on the publication, Crosslinking of a pos-
itive-tone, polynorbornene dielectric that was
selected for exchange with MURJ. An accom-
plished undergraduate researcher, Helen has re-
ceived the Presidents Undergraduate Research
Award and the Intel Undergraduate Research
Opportunities Scholarship. She is also the Sec-
retary for the Society of Women in Electrical and
Computer Engineering.
Zach is in his ffth year at Georgia
Tech pursuing a degree in Chemi-
cal and Biomolecular Engineer-
ing and a minor in Computer Sci-
ence. He is also working in the
Kohl group and is a co-author on
the Li paper. Zachs current research is focused
on improving microelectronics packaging and
fabrication. As a chemical engineer, his research
involves engineering materials with precisely
controlled electrical and mechanical properties.
In the fall of 2014 he will be starting his PhD in
Chemical Engineering. Zach is a member of the
Chemical Engineering Honor Society and plays
trombone in the Georgia Tech Marching Band.
Helen Li Zach Pritchard
IN THIS ISSUE
Societal influences on homosexual rights
In order to examine factors that impact
the level of homosexual rights, this pa-
per studied the relationships between
homosexual rights, womens infuence
beyond the domestic setting, cultural
views on children and marriage, and sex-
ually transmitted illnesses (STI) educa-
tion. Using data from 195 countries, high levels of womens
infuence and low levels of traditional views on children and
marriage were signifcantly correlated with high levels of ho-
mosexual rights. These conclusions suggest that improving
womens rights and challenging strict cultural norms on mar-
riage could lead to an improvement in homosexual rights.
Article p64
Obamacare and small business in America
The Patient Protection and Afordable Care Act (PPACA) is
providing Americans equal access to high quality, aford-
able healthcare. Designed to aid all Americans, the PPACA
has unintended consequences on small and medium-
sized businesses, such as growth limitations, and limited
cost control regulations. Despite the presence of these is-
sues, secondary solutions can be drafted and implement-
ed to reduce the impact on these businesses. Lacayo and
Davis-Nozemack examine and propose solutions to solve
and mitigate the associated challenges with the most sig-
nifcant regulatory overhaul of the US healthcare system.
Article p46
Generating polymers for tissue engineering
Biocompatible hydrogels have many ap-
plications, from acting as a medium for
drug and gene delivery to its use as an
environment to promote cellular growth.
Several structural proteins are present
within a human cells environment to al-
low for cell-to-cell communication and
diferentiation. Cui et al. have synthesized polymers to mimic
the function of these proteins for incorporation into hydro-
gels. They demonstrate that their synthesized polymers have
low toxicity and highly well-controlled dimensions. Their
work will further fuel investigation into biocompatible hy-
drogels for cell and tissue engineering applications.
Article p82
Immigration attitudes in the United Kingdom
In recent years Europe as a whole has un-
dergone a shift in immigration. Germany,
France, and Italy have all experienced
signifcant increases in the number of
immigrants they receive each year, but
their attitudes towards immigrants have
remained rather stable. On the other
hand, the United Kingdoms attitude towards immigrants
has drastically changed, despite little change in the number
of immigrants. This study examines unemployment levels
and immigration policy as potential causes for the diferent
attitudes.
Article p56
Signal integrity in digital circuits
Signal integrity is critical to the perfor-
mance of any electronic device, yet
nearly all metal circuit board compo-
nents exhibit intrinsic noise. Thus, it
is important to minimize fuctua-
tions from noise to prevent signal
degradation. Minimizing the change in current can improve
signal integrity and avoids reducing the noise of individual
circuit board components. Therefore, an encoding scheme
was designed to fnely control the most power-consuming
states in digital systems. As a result, the scheme reduced cur-
rent variation, greatly improving signal integrity and reduc-
ing power consumption.
Article p76
GTTOWER.ORG | 13
Collaboration is essential in research
felds for exchanging ideas, sharing
results and working to fll gaps in
knowledge. The Tower was founded
on this core belief with a particular
emphasis on undergraduate research
at Georgia Tech. Recently, The Tower
has endeavored to share and promote
Georgia Tech undergraduate research
on a national stage. One way we went
about this goal was to form article
exchange partnerships with peer in-
stitutions such as the Massachusets
Institute of Technology (MIT). Both
Georgia Tech and MIT are among the
nations leading research universities,
consistently providing vital research
and innovation to Americas gov-
ernment, industries and businesses.
Equally important, Georgia Tech and
MIT highly encourage undergradu-
ates to participate in faculty-lead
research in order to supplement stu-
dents technologically-based educa-
tions.
The Tower and the MIT Under-
graduate Research Journal (MURJ)
fundamentally believe in promoting,
inspiring and showcasing under-
graduate research. Thus, the goals
of The Tower-MURJ article exchange
program are to foster continued com-
mitment to undergraduate research
endeavors and research collabora-
tions between Georgia Tech and MIT.
Both journals had been discussing
the details and logistics of the article
exchange program for the past two
years, with a formal implementation
of the program in the summer of 2013.
As part of the program, the Editorial
Boards of both journals will pick one
article from their submissions pool
to exchange with, and publish in the
other journal. The chosen articles re-
fect high quality undergraduate re-
search from any major academic feld
recognized by Georgia Tech and MIT.
The selection of an article for the ar-
ticle ex-change program is highly
competitive and prestigious due to
the volume and quality of submis-
sions received by both journals each
semester. The article exchange will
occur every semester for each issue of
The Tower and MURJ published.
Both founded in 2007, The Tower
and MURJ share highly similar and
complementary publication philoso-
The Tower-MURJ
article exchange
program will make
authors from MIT
and Georgia Tech
visible to a national
audience
NEWS
1
School of Chemistry & Biochemistry, College of Sciences, Georgia Institute of Technology.
Correspondence should be addressed to AB (abanerjee38@gatech.edu).
Under gr aduat e r es ear ch
j our nal s pat t er n t o f os t er
under gr aduat e r es ear ch
Amrita Banerjee
1
The Tower and the MIT Undergraduate Research Journal form
a publishing collaboration to inspire, showcase and promote
undergraduate research.
NEWS
phies. Open-access publishing and
peer-review are core pillars of our
organizations. MURJ has received an
enormous amount of publicity in the
past several years due to the publi-
cation of its highly qualifed articles.
Recent volumes have featured leters
of introduction from MIT President
Susan Hockfeld, Institute Professor
Bob Langer, and Dean Kim Vandiver.
Similarly, The Tower has recently been
accepted into the collection of the US
Library of Congress as recognition of
its high quality articles. An Android
application currently in development
will expose The Towers content to a
national and global audience, and
mark The Tower as the frst under-
graduate research journal to have a
mobile application. The Tower also en-
joys strong relationships with the Un-
dergraduate Research Opportunities
Program (UROP) ofce and academic
departments around Georgia Tech.
The inaugural articles exchanged
between The Tower and MURJ feature
work from a research collaboration
between Georgia Tech and MITthe
NSF-funded, Emergent Behavior of
Integrated Cellular Systems Center
(EBICS). Georgia Tech and MIT were
the founding institutions of EBICS for
the purpose of engineering multicel-
lular biological machines that have
desired functionalities and can per-
form prescribed tasks. MIT under-
graduate, Kiara Cui participated
in a summer research experience
through EBICS and worked in
Dr. Paula Hammonds lab. Her
paper entitled, Synthesis of
Polypeptides for Hydrogel
Vertically-Integrated Projects (VIP) is a
multi-disciplinary undergraduate ed-
ucation program housed in the School
of Electrical and Computer Engineer-
ing at the Georgia Institute of Tech-
nology. Its goal is to foster innovative
thinking and entrepreneurial behav-
ior by involving students in challeng-
ing projects. VIP accomplishes this by
providing project-based learning for
undergraduates. Participants include
over 190 undergraduate students, 25
faculty members, and dozens of grad-
uate students. With over 19 diferent
teamsranging from BioBots, a team
creating microrobots that can traverse
biological barriers, to eDemocracy, a
team aiming to increase participation
in democratic dutiesyou will fnd
anyone from biology to mechanical
engineering to public policy majors
atending team meetings.
VIP started when Professor Ed-
ward Coyle brought over the pro-
gram from Purdue University when
he joined Georgia Tech in 2008. Each
team consists of several undergradu-
ates from diferent backgrounds, a
Ver t i cal l y- I nt egr at ed Pr oj ect s
s uppor t s t udent i nnovat i on
Jessica Block
1
1
School of Electrical and Computer Engineering, College of Engineering, Georgia Institute of
Technology. Correspondence should be addressed to JB (jessicat.block@gmail.com).
Scafolds was selected by the MURJ
Editorial Board for publication in Vol-
ume VI, Issue I of The Tower.
The Tower-MURJ article exchange
program will make authors from MIT
and Georgia Tech visible to a national
audience. They will be able to receive
collegiate feedback on their research
and be aforded the opportunity for
potential research collaborations. Dr.
Chris Reaves, Director of the UROP
ofce at Georgia Tech cites that the ar-
ticle exchange program will further
bridge our institutions and foster un-
dergraduate research. As The Tower
and MURJ embark on the next chapter
of their organizations history, we are
proud and excited to lead a new era
of undergraduate research publishing
together.
Faculty inspired Vertically-Integrated Projects are inspiring a new
paradigm of undergraduate education and learning outside the
classroom.
GTTOWER.ORG | 15
few graduate students to lead and
mentor, and a professor. The team has
a project based around a professors
idea or interest. This difers from the
normal curriculum because profes-
sors bring not only their knowledge
but their enthusiasm to the projects
explains Professor Randal Abler, team
leader and one of the original VIP
founders. He describes his own mo-
tivation as having something unique
to ofer and translate that into a class
at the undergraduate level is very rare
and usually seen more at the graduate
level.
Some of the projects beneft Geor-
gia Tech students daily. The Intelli-
gent Tutoring System (ITS) run by Dr.
James McClellan facilitates learning
for hundreds of students every se-
mester enrolled in ECE 2026: Intro-
duction to Digital Signal Processing.
ITS was developed by Dr. McClellans
VIP team to provide an online tutor-
ing system that adapts to the needs
of the student, generates concept-fo-
cused questions and suggests areas
for further improvement. Professor
Clay Phillipss eCampus team devel-
oped a mobile application for Geor-
gia Tech students to swap textbooks.
With the help of students from com-
puter science, industrial engineer-
ing, and business administration, the
Intelligent Transportation Systems
team has taken on the challenge of op-
timizing the Tech Trolleys routes and
arrival predictions. Other teams, such
as eStadium, have strong industry
contacts with companies including
Texas Instruments, National Instru-
ments, and Cisco.
The VIP program enables under-
graduates to atend conferences, de-
velop products, and maintain indus-
try relationships. Participation in
VIP forces one to work outside of their
disciplines comfort zone resulting in
new ways of thinking about problems
and collaborations that would not
otherwise exist, explains Jef Bair, a
Georgia Tech and VIP alumnus. VIP
ofers real world experience and tools
for long-term success. It taught me
the value of keeping careful notes
during development and debugging.
That skill has come in handy else-
where, says Hunter Scot, an alum-
nus who participated in three difer-
ent teams over two and a half years.
[This program] let me mess around
with embedded systems before I had
the prerequisites to take any classes
on it, which was prety neat. Later
when I could take those classes, hav-
ing seen it before made things a bit
easier.
The VIP program ofers some-
thing diferent than normal semes-
ter projects. The problems are open
ended without a known solution and
it ofers continuity from semester
to semester. For instance, the group
BrainBeats develops hardware and
conducts human subject experiments
to determine how a human follows
rhythm. They are interested in the
diference between a person who can
tap their foot to the beat of a tune and
another human who lacks this ability.
VIP ofers a platform to search for an
answer to this fundamental question.
As Massive Open Online Courses
(MOOCs) continue to become more
mainstream in large universities,
programs like VIP that ofer project-
based learning will become a neces-
sity. MOOCs are very cost-efective
and efcient in translating knowledge
to students. However, team work and
hands-on projects, both important
components of learning, are missing.
VIP and MOOCs complement each
other, each ofering important experi-
ences in educational development.
Inspired by Georgia Techs VIP
Program, universities all around the
globe have incorporated similar pro-
grams into their own schools. Since its
start, VIP has expanded internation-
ally to six universities including Na-
tional Ilan University in Ilan, Tawian;
University of Strathcldye in Glasgow,
Scotland, UK; University of Michigan
in Ann Arbor, MI; and Morehouse
College in Atlanta, GA.
VIP can be used as credit towards
graduation requirements for most
majors at Georgia Tech. To learn more
or complete an application visit vip.
gatech.edu.
NEWS
...the goal is to foster
innovative thinking
and entrepreneurial
behavior by
involving students in
challenging projects
NEWS
It turns out that the old adage, never
return to the scene of the crime is
not necessarily true within criminal
communities. In terms of burglary,
a house is more likely to be burgled
twice than once. Furthermore, bur-
glary happens in clusters; a house is
more likely to be burgled if a nearby
house has been burgled. Any stu-
dent who has had the (dis)pleasure
of taking a diferential equations class
should be reminded of the mathemat-
ics governing springs when confront-
ed with this sort of positive feedback.
As Georgia Tech Assistant Profes-
sor in the School of Mathematics Dr.
Martin Short explains, modeling a
system as complex as criminal behav-
ior is remarkably similar to modeling
a spring.
Modeling a distribution of burglar-
ies, which has a spatial and temporal
patern of positive feedback, Dr. Short
utilizes a series of ordinary diferen-
tial equations. The results of his mod-
el can be indicative of either super-
or sub-critical criminal hotspots.
A super-critical result im-
plies that the slightest criminal per-
turbations will excite a new criminal
hotspot. For example, a police crack-
down on a super-critical hotspot will
eliminate the hotspot, yet in the pro-
cess some crime will leak into the sur-
rounding areas, which in turn excites
new crime. Due to the super-critical
nature, new criminal hotspots will
emerge from these police perturba-
tions. Conversely, sub-critical crimi-
nal hotspots will not evolve into new
hotspots if perturbed. Eliminating
a sub-critical hotspot will result in a
lasting reduction in crime.
Dr. Shorts model provides a
shocking reality; in theory, the mod-
el claims that police activity might
be futile in some cases, yet infuen-
tial in others. Thus, the pressing and
important question for investigation
is, what makes some areas super-
critical and others sub-critical? Sup-
plied with observations of criminal
network activity and mathematical
models of such networks, the answer
to this question turns out to greatly
depend on initial conditions. One of
the most important, yet least charac-
terized initial conditions is the rate of
crime.
Dr. Short sought to understand
the factors that determine a neighbor-
hoods crime rate in order to accurate-
ly and mathematically model criminal
behavior. He created a simple game
to represent diferent societal-based
initial conditions. In this game there
are two traits, willingness to testify to
a crime and willingness to commit a
crime. There also exists four charac-
ters, which are the manifestations of
these traits. An informant is both will-
ing to testify and commit a crime. A
paladin is willing to testify, but not
willing to commit a crime. A villain
is not willing to testify, but willing to
commit a crime. Finally, an apathetic
individual is not willing to testify, but
also not willing to commit a crime.
These characters are meant to classify
individuals within a society as the
best intentioned (paladins), average
intentioned (apathetic and informant)
and the worst intentioned (villains).

1
School of Mathematics, College of Sciences, Georgia Institute of Technology. Cor-
respondence should be addressed to CH (chrs.hrpr@gmail.com).
The mat hemat i cs of cr i mi nal
behavi or
Christopher Harper
1
A Georgia Tech researcher presents a novel, mathematical
approach to model, describe and predict criminal network
activity.
Visualization of simulated crime hotspots
with hot areas in red and cold areas in
purple. (Photo credit: Dr. Martin Short).
GTTOWER.ORG | 17
NEWS
Using this simplifcation of society,
Dr. Short constructed a mathemati-
cal model to determine crime rates in
neighborhoods. The initial conditions
for the model were the proportions of
the population that pertained to each
of the four character classifcations.
The results were shocking. When try-
ing to reach a state of utopia, the most
important initial condition was the
number of informants in the neigh-
borhood. More informants lowered
crime rates and caused a criminal
hotspot to become sub-critical in na-
ture.
In addition to working on criminal
hotspots, Dr. Short has worked on in-
creasing the accuracy of crime predic-
tion, studying gang territoriality and
retaliatory violence, and many other
crime related topics. He has pub-
lished numerous times, the most re-
cent being Modeling crime difusion
and crime suppression on transporta-
tion networks in the AAI Symposium
on Social Networks and Social Contagion
in 2013. Dr. Shorts research covers
a variety of topics, so just remember
the following: people do return to the
scene of the crime, suppressing crime
could be like squashing a roach or an
infuriating game of whack-a-mole,
and to help reduce crime dont be a
hero - just be average!
The world of particle physics has en-
dured over ffty years of uncertainty
revolving around the postulated ex-
istence of the mystical Higgs boson.
The Higgs boson, the particle that
provides mass to everything in the
universe, has perplexed the scientifc
community since Dr. Peter Higgs frst
proposed his theory governing the
particle in 1964.
Classical physics had gradually
progressed over centuries towards
I t al l mat t er s
The di s cover y of t he Hi ggs bos on
Ravi Konjeti
1
1
George W. Woodruf School of Mechanical Engineering, College of Engineering, Georgia
Institute of Technology. Correspondence should be addressed to RK (ravikonjeti@gmail.com).
The discovery of the Higgs boson is considered one of the most
signifcant discoveries in particle physics in the past 20 years.
However, the Higgs has spurred more scientifc questions than
provided answers.
understanding the universe at smaller
and smaller scopes. The once-satisfy-
ing molecular frame slowly became
unsatisfactory for understanding the
origins of mater and the physics of the
universe. Atoms and subatomic par-
ticles became the simplest structures
known. However, during the early
1960s, the Standard Model of particle
physics was proposed and stated that
quarks and neutrinos comprise basic
subatomic particles, such as electrons
and protons. Defned as elementary
particles and fundamental constitu-
ents of mater, quarks and neutrinos
provide a rough understanding of
basic physical phenomena, such as
forces and mass. They provide fur-
ther avenues to investigate the ingre-
dients of our universe, however they
do not complete our understanding
of physical phenomena. The equa-
tions stated by the Standard Model
accurately defned quantum physics
with one catch: all the particles were
assumed massless. The symmetrical
characteristics disappeared once the
equations were modifed to account
for the masses of the particles, making
the entire model a perplexing puzzle;
that is, until Dr. Higgss theories on
the Higgs boson and the Higgs feld.
Dr. Higgs suggested that the en-
tire universe worked under the in-
fuence of the Higgs feld, which
provides mass to all objects that accel-
erate within it. The Higgs feld allows
for quantum mechanics equations to
hold and account for particle masses.
However, the Higgs boson had not
been experimentally verifed until re-
cently. Ironically so, Dr. Higgss work
NEWS
was not well received when he frst
proposed his theory. After moving to
Edinburg University, he spent a great
deal of time investigating the exis-
tence of mass and weight. After years
of postulating, he fnally had derived
the necessary equations with a mag-
nifcent mechanism that later became
known as the Higgs feld. He submit-
ted his work to the globally-renowned
Conseil Europen pour la Recherche
Nuclairein (CERN) and it was later
published. Yet, the paper was hidden
and unnoticed by the larger physics
community. He wrote a second paper
years later and sent it back to CERN
for publication, but this time the pa-
per was rejected, quoting no realistic
physics knowledge. Dr. Higgs then
sent the paper to an American phys-
ics journal, which provided his theo-
ry the exposure it needed. Likewise,
another physicist Dr. Franois En-
glert had published similar fndings,
providing additional publicity. Thus,
a scientifc endeavor began to prove
the reality of the Higgs feld through
discovering the Higgs boson, which
interacts with the feld.
In March 2013, the race to fnd
the boson came to a head when re-
searchers at CERN announced they
had discovered the existence of a
fundamental particle that holds
all similarities to that of the
Higgs boson. A month later
CERN was able to confrm
that in fact the Higgs boson had been
found using the Large Hadron Col-
lider, the worlds largest and most
expensive particle collider. However,
the discovery has not caused com-
plete rejoice because the boson could
not be consistently detected in repeat
experiments. Despite the inconsistent
fndings, the found bosons charac-
teristics were accurately predicted by
the Standard Model. In fact, recently
the proposal has surfaced that there
may be up to fve unique Higgs bo-
sons and the scientifc community has
only found one of them. Nonetheless,
in October 2013, Dr. Higgs and his
colleague Dr. Franois Englert both
won the Nobel Prize in Physics for
their work in understanding the un-
derlying mechanisms that control the
mass of objects.
The extent of the knowledge in
discovering the Higgs boson is still
waiting to unfold. The discovery has
not had any practical implication for
the greater society; however, scientists
say that it will not be long before uses
are found. Arguing that prior quan-
tum fndings have quickly morphed
into products such as the World Wide
Web and the transistor, CERN is un-
deterred that the Higgs boson fnding
can allow for further exploitations of
the garnered knowledge. With a total
investment exceeding $13 billion just
at CERNs Larger Hadron Collider,
scientists want to further expose the
inner workings and fnd keys to un-
covering the particles of dark mater.
Graphical representation of a Higgs boson decaying to two tau particles in the ATLAS
detector. (Photo credit: CERN).
...there may be up to fve Higgs bosons and
the scientifc community has only found one
of them.
GTTOWER.ORG | 19
As an undergraduate researcher in Dr. Al
Merrills lab, Christine investigated de-
tecting and quantifying biomolecules us-
ing custom mass spectrometry techniques
for potential diagnostic applications. Her
publication in The Tower highlights the use
of novel mass spectrometry techniques to
study the activation of infammatory pathways. Currently a
graduate student at Johns Hopkins, Christine is studying how
to diagnose and treat diseases of the cardiovascular system on
the molecular level, and working to improve instrumentation
used to identify biomarkers of such diseases. She was award-
ed a pre-doctoral training grant by
the National Heart, Lung, and Blood
Institute to fund her research. After
completing her masters degree at
Hopkins, Christine will begin training
for an MD/PhD to be at the forefront
of cardiovascular research and to pro-
vide patients with the most advanced
medical care available.
Kyle worked on an
interdisciplinary
team as a comput-
er science major
to research how
to efciently route
package-carrying vehicles through a ship-
ping warehouse while avoiding collisions. He approached
the problem from a theoretical standpoint in an atempt to
establish performance metrics of routing efciency. His team
partnered with two companies in industry to develop func-
tional prototypes of his routing algorithms. They published
preliminary results of this research in The Tower and cur-
rently preparing another paper for a peer-reviewed journal.
The experience performing this research, Kyle notes, has been
incredibly invaluable for his academic and professional ca-
reers. He secured internship positions at Palantir and Face-
book with the skill sets he developed as a researcher. Kyle
has accepted a position and will start working full-time as a
software engineer at Facebook this summer.
Martin will gradu-
ate in May 2014
with a bachelors
degree in phys-
ics and a minor
in chemistry. He
previously worked with Dr. John Wise in
the School of Physics investigating the cosmic origins of our
universe. His publication in The Tower was the feature work of
Volume V, Issue II and detailed his research on modeling the
formation of primordial galaxies through astrophysical simu-
lations. Martin is currently investigating Amyotrophic Lat-
eral Sclerosis (ALS) in Dr. Cassie Mitchells neuroengineering
lab in the Department of Biomedical Engineering. In the sum-
mer of 2014, he will begin an MD/PhD program, with plans
to focus his PhD in either Biomedical Engineering or Nuclear
& Radiological Engineering at Georgia Tech. With dual doc-
torate degrees, Martin seeks to pursue a career in medical re-
search, striving to combine his passions for physics, computer
science, and medical engineering.
Michael is a third year economics and in-
ternational afairs double major at Geor-
gia Tech. He has always been interested
in economic policy and hopes to pursue
a career in a related feld. During his time
at Georgia Tech, he has worked on a presi-
dential campaign and two congressional
campaigns. Last spring he worked as an intern in the House
Majority Caucus Ofce in the Georgia State Capitol and is
currently a legislative aide in the Capitol. He is also the Politi-
cal Director for a US congressional campaign. Although busy
with academics and impressive work experiences, Michael
still fnds time to volunteer; he is a
Young Life leader at Whitfeld Acad-
emy, Chairman of the College Repub-
licans at Georgia Tech and chairs the
alumni fundraising eforts at Mt. Pis-
gah Christian School.
Michael de la Guardia
Martin Halicek Kyle Davis
Christine Amuzie
Previ ous
A u t h o r s
We spotlight four previ-
ous authors in The Tow-
er who are also some of
the brightest students
at Georgia Tech
Keith McGreggor is an entrepreneur, visionary and
mentor currently supporting student and faculty in-
novation at Georgia Tech. He is the Director of the
Georgia Tech VentureLab, a globally ranked busi-
ness and start-up incubator. Over his 30 year career,
McGreggor has had an unbounded curiosity for
high-technology, entrepreneurial spirit, and natural
potential for leadership and problem solving. His
drive, talent and abilities set him on a path to start
six companies and work for some of the worlds
most infuential technology corporations.
McGreggor graduated with a bachelors and
masters degree in computer science from Georgia
Tech. In the 1970s he saw a great op-
portunity in the then-nascent felds
of computer science and computer
engineering. He wrote the frst ever
3D game prototype for the Macin-
tosh OS, which caught Apples aten-
tion. He was hired by Apple as one of
their original employees and led the
graphics group for three years. Dur-
ing that time, McGreggor developed
the frst graphics editor for a com-
puter operating system that defned
color architecture and management.
He has three US patents to his name because of this
technology. In fact, if you use a laptop, tablet, cell
phone, or television then chances are that you are
using the color technology he created.
Shortly after his time at Apple, McGreggor
started a company focused on artifcial intelligence.
Lockheed Martin bought his company to engineer
customized robotic systems for military applica-
tions. Over the next several years he had created
fve other software start-ups that ranged from enter-
prise document management applications to robust
security software, and from fractal video compres-
sion algorithms to platforms for internet television.
McGreggor also served as the Chief Technology
Ofcer and Director of Engineering at Yahoo! for
nearly a decade.
Over his entire career McGreggor has had a
theme of creating start-up companies and, as he
notes, geting bored. His curiosity and excitement
continuously drove him for new business and tech-
nology ventures. He setled back at Georgia Tech to
become Director of the VentureLab and share his
entrepreneurial expertise with new, fedgling stu-
dents that seek to bring ideas to market. McGreg-
gor greatly enjoys interacting with students because
he wants to help others make an impact. His move
back to Georgia Tech was exhilarating because he
was able to rediscover himself. In fact, he is pursu-
ing and close to fnishing a PhD in computer sci-
ence.
Understanding yourself and defning your
skills are essential components, (soon to be Dr.) Mc-
Greggor argues, for the fabric of innovation of a
start-up company. Successful entrepreneurs trans-
late the characteristic get it done engineering ati-
tude into a viable business. The VentureLab and Dr.
McGreggor provide the consulting and resources in
order to develop a business model based around a
product or innovation with a market need. In his
perspective, student are usually anxious to get their
frst job after graduation. However, starting a busi-
ness requires clarity and focus on multiple intellec-
tual fronts.
Dr. McGreggor takes a unique approach to
building start-up ventures. Compared to other uni-
versities, the VentureLab lets the market triage tech-
nologies that they receive. Thus, students are frst
tasked with fnding potential consumers for prod-
ucts they seek to bring to market. In this light, Dr.
McGreggor views his job as more creation coach-
ing, rather than business development.
Despite the extensive list of companies he has
created and worked for, Dr. McGreggor consid-
ers his job at Georgia Tech to be the best job he has
had in his 30 year career. Since he joined the Ven-
tureLab, more than 150 companies have been cre-
ated that have in turn raised $700 million in angel
and venture capitalist funding. He is a true titan of
industry and, more importantly, a highly valuable
mentor and inspiration for the entire Georgia Tech
community.
INTERVIEW
Kei t h McGr eggor
Keith McGeggor
Making entrepreneurship accesible to all
GTTOWER.ORG | 21
amec.com
Shaping the Future
We are hiring new graduates from all
engineering and science disciplines
AMEC is a leading supplier of consultancy, engineering and project
management services to our customers in the worlds oil and gas,
mining, clean energy, environment and infrastructure markets.
Come join our team!
Visit www.amec.com/careers for more information
on these positions or to submit a resume.

Joseph Elsherbini
1
Open acces s f or our gener at i on
Imagine atending a university where you were
expected to teach full time while paying tens
of thousands of dollars in tuition. Your fel-
low students graded your work, and less than
10% of the students in the school graduated.
Then, if you were one of the lucky ones who
did pass, your teaching would be recorded on
video tapes and sold back to other students on
a subscription basis, while the publisher pock-
eted the profts. Welcome to the current state of
academic publishing.
A handful of publishing companies (most
notably Elsevier, Wiley, and Springer, which
accounted for 42% of the market in 2012) own
a signifcant portion of academic journals. The
research published in these journals is largely
funded by taxpayer dollars through grants
awarded by federal organizations, such as the
National Institutes of Health (NIH) and the Na-
tional Science Foundation (NSF). The articles
are subjected to a rigorous peer review process,
which professors do for free on their own time.
Then this work, usually a product of years of
federal funding and work by graduate students
and professors, edited and reviewed by other
professors for free, is handed over to the jour-
nals and put behind a paywall. Elsevier (by far
the largest of the publishing companies) posted
profts of over $720 million in 2011, with an
astounding proft-margin of 36% (Academic
publishing, 2011).
1
School of Biology, College of Sciences, Georgia Institute of Technology. Correspondence should be addressed to JE
(jelsherbini@gatech.edu).
Currently the research being paid for by US
taxpayers is siting behind a paywall. Despite
that the majority of academic research in the
US is performed by students and professors,
publishing companies are earning huge prof-
its. The open access movement seeks to trans-
form the academic publishing ecosystem from
proft-driven and exclusive to knowledge-
driven and open. The vision, impact, chal-
lenges and future outlook of open accessing
publishing is examined with respect to fur-
thering scientifc advancement and improving
the academic publishing landscape.
PERSPECTIVE
GTTOWER.ORG | 23
The peculiarities of the academic publishing system
have long been known and reported, yet solutions have
only been recently presented. The Open Access move-
ment, starting in the year 2000 (Butler, 2003), as well as
the many publications from the library world admonish-
ing the rising costs of maintaining academic subscriptions
(Bosch, Henderson, & Klusendorf, 2011) (Ivins, 2005),
have sought to raise awareness of this issue and to create
solutions. The Information Age and the new generation of
scientists trained during this time are uniquely positioned
to infuence the course of academic publishing from prof-
it-driven and exclusive to knowledge-driven and open.
A brief history of academic publishing
In the early 17th Century, the scientifc journal as we
know it did not exist. Scholars like Isaac Newton and Rob-
ert Hooke often published their discoveries in code, so
that if anyone else made the same discovery, they could
decode the message and prove that they had discovered
it frst (Hall, 2002). Scientists published infrequent, large
volumes of their work. The frst academic publication
wholly devoted to science was the Philosophical Transac-
tions of the Royal Society, (Oldenburg, 1665). This marked
the beginning of a transition of publishing shorter, more
frequent articles on current work rather than waiting for
a whole books worth of material before publishing. This
trend continued as scientists became more professional-
ized and needed proof of productivity in order to stay in
the good graces of their employers.
In the United States, by the turn of the 20th century,
most research was published through non-proft univer-
sity presses or scientifc societies. It was not until the 1970s
that there began a large trend for the more successful
non-proft publications to be bought by for-proft institu-
tions. (Elsevier, 2005) Throughout the decades, the aver-
age price of a journal subscription steadily grew at a rapid
pace (Townsend, 2003). The primary consumers of these
publications were the academic institutions themselves.
In 2002, 65% of Elseviers customers were academic insti-
tutions. (Gooden, Owen, & Simon, 2002). The rising costs
of subscriptions came at the same time as the budgets of
academic libraries were being cut. These two issues came
to a head in the early 2000s in what is known as the Seri-
als Crisis (Young, 2009; Panitch & Michalak, 2005). Most
recently the issue was brought to national atention when
Harvard University announced that it could not sustain
its academic subscriptions, which was close to 3.75 million
dollars a year (Faculty Advisory Council, 2012).
Peer review: What is it good for?
In todays publishing landscape, articles are subjected to
rigorous peer review. This rigor is intended to flter bad
papers out, and to give suggestions for mediocre papers
to improve. This review is usually double-blind, meaning
both the authors reviewers names are unknown to the
other party. However, as felds become more and more
specialized, the list of peers a journal can call on for a given
paper could be extremely small. This can lead to situations
where either direct competitors are reviewing each others
work before publication, or the reviewer is not truly an ex-
pert in the feld. There have been many articles and much
discourse (Higgs 2007; Horton, 2000; Rennie D, Flanagin
A, Smith R, & Smith J, 2003) on the efcacy of peer review
in judging the merits of a paper. One article posits that the
rigorous peer review process produces journals exclusive
in participation, innovation averse, few in number, out-
dated in content, restricted in scope, largely unread and
increasingly specialized (Whitworth & Friedman, 2009).
The open access movement
The Public Library of Science (PLoS) was founded in 2000.
Founders Harold Varmus, the director of National Can-
cer Institute; Patrick Brown, a professor at Stanford Uni-
versitys Medical School and an investigator at Howard
Hughes Medical Institute in California, and Michael Eisen,
a professor at UC Berkeley wrote an open leter to the sci-
entifc community, urging researchers to only publish
their work in journals that made the full free text of their
articles available within six months of publication (Early
History | PLoS, n.d.). Over 34,000 scientists signed the
leter, but changes were not evident in the years immedi-
ately following. So in 2003, PLoS launched its frst open
access journal, PLoS Biology.
Ten years later, the Directory of Open Access Journals
PERSPECTIVE
(DOAJ) lists 9,948 fully open journals, over half of which
are searchable at the article level on its webpage (DOAJ:
Directory of Open Access Journals, n.d.). However, this
rapid and impressive growth has not come without its
share of criticism. In order to raise money for publishing
and operating costs, most open access journals require a
publication fee to be paid for by the author. Critics claim
that the less prestigious of PLoSs oferings are extremely
lenient in their review process in order to generate more
revenue, in other words researchers are paying to be pub-
lished when no other peer-reviewed journal would have
let them in.
Whether or not these allegations are true, the efect
that the open access movement has had on the industry
is undeniable. In 2008, NIH released a statement requir-
ing all research funded through it to be made open access
within a year of its publication. At the time this was a huge
step for the open access movement. This year in Febru-
ary the White House released a memorandum that all re-
search funded through federal organizations with budgets
of over 100 million dollars would be held to the same one
year open access deadline (Holdren, 2013). Many mem-
bers of the open access movement, including one of the
founding members of PLoS Micheal Eisen, see this as a
step backward, in efect codifying the 1 year embargo pe-
riod that publishing companies enjoyed from NIH funded
grants (Eisen, 2013). Others see it is a stepping stone to
eventually requiring full open access.
Current issues with open access journals
Open access scientifc journals have mushroomed into a
global industry, driven by author publication fees rather
than traditional subscriptions. This business model often
promotes predatory publishing and an incentive to in-
crease publication volumerather than qualityin or-
der to be proftable. Thus, concerns have arisen over the
scrutiny of the peer-review process at many open ac-
cess scientifc journals. In a recent sting operation con-
ducted by the prestigious, subscription-based journal,
Science, several open access journals had litle to no
quality control of manuscripts submited for publi-
cation (Bohannon 2013). Using an alias, a member
of the Science Editorial Board submited a bogus scientifc
paper with obvious experimental faws to 304 open access
journals around the globe. An astonishing 52% of the jour-
nals had ultimately accepted the paper for publication. Of
the 255 papers that underwent the entire editing process
to acceptance or rejection, about 60% of the fnal deci-
sions occurred with no sign of peer review, likely with-
out the papers being read by anyone. Of the 106 journals
that discernibly performed any review, 70% ultimately ac-
cepted the paper. Most reviews focused exclusively on the
papers layout, formating, and language. Nonetheless,
reputable journals like PLoS had not only raised the issue
of the papers scientifc quality, but also meticulously in-
quired about studys institutional review and documenta-
tion. The Science study reveals the need for more stringent
oversight and publishing regulations for the emerging
open access publishing enterprise. Ensuring that journals
honor their obligation to peer-review is a challenge that
the scientifc community must rise to because journals
without quality control are simply destructive for the ad-
vancement of science.
A vision for the future
It can be argued that the current peer-reviewed, pub-
lisher controlled system of sharing scientifc discovery
has served to standardize article writing. Nevertheless,
this system has inherently unfair economic consequences.
When public funds are used to generate research, then
that research should be immediately available to the pub-
lic. It is important for our generation of scientists to realize
that the scholarly publishing industry as it is today has
not always been in place. We have to come together and
fgure out solutions so that our libraries can aford to carry
the work we ourselves are producing. We, more than ever
before, have the power to choose where and how our re-
search is published, and who has access to it. We need to
change the culture that values the title of the journal in
which a work is published and instead value the content
of the work itself. We need to evaluate the peer-review
process and make sure that it still makes sense in the face
of having access to faster media with huge potential for
collaboration and large-scale communication. A Morgan
PERSPECTIVE
GTTOWER.ORG | 25
Stanley research team in a report from 2002 urging the
continued investment in Elsevier writes, The nature of
the scientifc publishing industry will not change any time
soon, in our view, despite the atempts [...] to encourage
academics to publish their research directly on the internet
and to encourage the boards of individual journals (who
peer review the scientifc articles included in journals) to
defect from commercial publishers to not-for-proft pub-
lishers (Gooden, Owen, & Simon, 2002). I hope, more
than ten years after this report was writen, our generation
of researchers can start to prove them wrong.
References
1. Albert, K. M. (2006). Open access: implications for scholarly pub-
lishing and medical libraries. Journal of the Medical Library As-
sociation, 94(3), 253262.
2. Antelman, K. (2004). Do open-access articles have a greater re-
search impact? College & research libraries, 65(5), 372382.
3. Bohannon J. Whos afraid of peer review?. Science.
2013;342(6154):60-5.
4. Bosch, S., Henderson, K., & Klusendorf, H. (2011, April 1). Periodi-
cals Price Survey 2011 | Under Pressure, Times Are Changing. Re-
trieved October 5, 2013, from htp://lj.libraryjournal.com/2011/04/
publishing/periodicals-price-survey-2011-under-pressure-times-
are-changing/
5. Butler, D. (2003). Scientifc Publishing: Who will pay for open ac-
cess? Nature, 425(6958), 554555.
6. DOAJ: Directory of Open Access Journals. (n.d.). Retrieved Octo-
ber 5, 2013, from htp://www.doaj.org/
7. Early History | PLOS. (n.d.). Retrieved October 5, 2013, from htp://
www.plos.org/about/what-is-plos/early-history/
8. Eisen, M. (2013, February). No celebrations here: why the White
House public access policy is bad for open access. Retrieved Octo-
ber 5, 2013, from htp://www.michaeleisen.org/blog/?p=1312
9. Elsevier. (2005). A Short History of Elsevier. Retrieved from htp://
cdn.elsevier.com/assets/pdf_fle/0014/102632/historyofelsevier.pdf
10. Eysenbach, G. (2006). Citation advantage of open access articles.
PLoS biology, 4(5), e157.
11. Faculty Advisory Council. (2012, April 17). Faculty Advisory
Council Memorandum on Journal Pricing THE HARVARD LI-
BRARY. Retrieved October 5, 2013, from htp://isites.harvard.edu/
icb/icb.do?keyword=k77982&tabgroupid=icb.tabgroup143448
12. Gooden, P., Owen, M., & Simon, S. (2002). Scientifc Publishing:
Knowledge is Power. Morgan Stanley Equity Research Europe.
Retrieved from htp://www.econ.ucsb.edu/~tedb/Journals/mor-
ganstanley.pdf
13. Hall, A. R. (2002). Philosophers at war: the quarrel between New-
ton and Leibniz. Cambridge: Cambridge University Press.
14. Harnad, S., & Brody, T. (2004). Comparing the impact of open ac-
cess (OA) vs. non-OA articles in the same journals. D-lib Magazine,
10(6). Retrieved from htp://eprints.ecs.soton.ac.uk/10207
15. Higgs, R. (2007, May). Peer Review, Publication in Top Journals,
Scientifc Consensus, and So Forth. The Independent Institute. Re-
trieved October 5, 2013, from htp://www.independent.org/news-
room/article.asp?id=1963
16. Holdren, J. (2013, February 22). Increasing Access to the Results of
Federally Funded Scientifc Research. Executive Ofce of the Presi-
dent. Retrieved from htp://www.whitehouse.gov/sites/default/
fles/microsites/ostp/ostp_public_access_memo_2013.pdf
17. Horton, R. (2000). Genetically modifed food: consternation, confu-
sion, and crack-up. Medical Journal of Australia, 172(4). Retrieved
from htps://www.mja.com.au/journal/2000/172/4/genetically-
modifed-food-consternation-confusion-and-crack
18. Ivins, O. (2005). The economics of scholarly publishing: Through a
glass, darkly. The Serials Librarian, 48(1-2), 102112.
19. McGuigan, G., & Russell, R. (2008). The Business of Academic
Publishing: A Strategic Analysis of the Academic Journal Publish-
ing Industry and its Impact on the Future of Scholarly Publishing.
Electronic Journal of Academic and Special Librarianship, 9(3).
Retrieved from htp://southernlibrarianship.icaap.org/content/
v09n03/mcguigan_g01.html
20. Oldenburg, H. (1665). Epistle Dedicatory. Philosophical Transac-
tions, 1(1-22), rstl.1665.0001. doi:10.1098/rstl.1665.0001
21. Panitch, J. M., & Michalak, S. (2005). The serials crisis: a white pa-
per for the UNC-Chapel Hill Scholarly Communications Convo-
cation. Chapel Hill, NC: University of North Carolina. Retrieved,
3(17), 2006.
22. Rennie D, Flanagin A, Smith R, & Smith J. (2003). Fifth interna-
tional congress on peer review and biomedical publication: Call for
research. JAMA, 289(11), 14381438. doi:10.1001/jama.289.11.1438
23. Sargent, J. (2013, April 19). Federal Research and Development
Funding: FY2013. Congressional Research Service. Retrieved from
htps://www.fas.org/sgp/crs/misc/R42410.pdf
24. Townsend, R. (2003, October). History and the Future of Scholarly
Publishing. Retrieved October 4, 2013, from htp://www.historians.
org/perspectives/issues/2003/0310/0310vie3.htm
25. Weber, R. (1999). The Journal Review Process: A Manifesto for
Change. Communications of the Association for Information Sys-
tems, 2(1). Retrieved from htp://aisel.aisnet.org/cais/vol2/iss1/12
26. Whitworth, B., & Friedman, R. (2009). Reinventing academic pub-
lishing online. Part I: Rigor, relevance and practice. First Monday,
14(8). Retrieved from htp://megafotos.ru/-NZam91cm5hbHMud-
WljLmVkdQ..ZN-ojs/index.php/fm/article/view/2609
27. Young, P. (2009). The serials crisis and open access. Technical
report, Virginia Tech. Retrieved from htp://scholar.lib.vt.edu/
faculty_archives/YoungP/OAwhitepaper.pdf?q=faculty-survey-
2009-key-strategic-insights-for-libraries
PERSPECTIVE
Lahari Shetty
1
& Francesca Storici, PhD
1
I nvol vement of RNas e H enz ymes
i n r i bonucl eot i de ext r act i on and
Ai car di - Gout i er es Syndr ome
The human body boasts countless defense and
repair mechanisms in order to catch the inevita-
ble mistakes that occur while working to main-
tain homeostasis. This practice is especially ap-
parent in DNA as there are numerous processes
that rectify errors during replication, transcrip-
tion, and translation. Ribonucleotide excision
repair (RER) is one of these important processes
in the cell. Ribonucleotides are integrated in the
DNA during replication or repair, but as ribose
is a signifcantly more unstable molecule com-
pared to deoxyribose due to its 2 reactive hy-
droxyl group, ribonucleotides increase the rate
of short deletions in the DNA by sensitizing the
DNA to enzymatic nicking [1, 2]. Ribonucleo-
tides can also alter the double helix structure of
DNA causing a change in DNA conformation
from the B form, with equally available major
and minor grooves in the double helix, to the A
form, with a deep major groove in the double
helix which could potentially afect DNA and
RNA polymerases ability to synthesize new
DNA or RNA from the parental strand [3, 4].
Therefore, without proper extraction of these
ribonucleotides, the cell could face major com-
1
School of Biology, College of Sciences, Georgia Institute of Technology. Correspondence should be addressed to LS
(lshety3@gatech.edu).
PERSPECTIVE
Ribonuclease H (RNase H) removes ribonucle-
otides from chromosomes, a process essential
to stabilizing the genome. Mutations in any
of the three RNase H subunits (RNASEH2A,
RNASEH2B, RNASEH2C) cause a serious neu-
rological disorder called Aicardi-Goutires
syndrome (AGS). AGS itself is a very rare ge-
netic disorder, but pathogenically resembles
acquired autoimmune diseases such as lupus
and congenital HIV infections. Illustrating
the genetics behind AGS could ultimately
elucidate the method of pathogenesis of these
aforementioned disorders as well. In this re-
view, we explore prior work investigating
mutated RNase H2 and discuss the necessity
of further studies on the over-expression of
mutant or wild-type RNase H2 and its down-
stream efect on cell growth and survival in
the presence of DNA damaging agents.
GTTOWER.ORG | 27
plications during DNA replication and repair. In RER,
Ribonuclease H (RNase H) performs this process that is
essential to stabilizing the genome. Therefore, it is of great
interest to examine how mutating and overexpressing
RNase H2 afects cell growth and survival in eukaryotes.
RNase H defciency in Aicardi-Goutires syndrome
When genes encoding RNase H develop a mutation that
afects RNase H2s function, a serious neurological disor-
der called Aicardi-Goutires syndrome (AGS), which has
symptoms resembling a brain viral infection, can devel-
op [5]. AGS can cause early progressive encephalopathy,
intercerebral calcifcations, and elevated levels of white
blood cells and interferon- in the cerebrospinal fuid [5,6].
Children having this disorder exhibit lack of progression
in motor, language, and social skills. AGS does not have a
cure at this time and the method of pathogenicity is still
uncertain [6]. AGS itself is a very rare genetic disorder,
but due to its pathogenic resemblance to acquired auto-
immune diseases such as lupus and congenital HIV infec-
tions, it is predicted that illustrating the genetics behind
AGS will ultimately elucidate the method of pathogenesis
of the aforementioned disorders as well [7].
Mutations in RNase H2 subunits
A recent study has identifed that mutations in any of the
three RNase H2 subunits (RNASEH2A, RNASEH2B, or
RNASEH2C) reduce enzymatic function and lead to AGS
[5]. Human and Saccharomyces cerevisiae, or bakers yeast,
genomes are largely homologous, thus most mechanisms
are predicted to be conserved across species. As a result,
S. cerevisiae is widely used as a model organism in mo-
lecular genetics research. There is some level of conserva-
tion between the human RNASEH2A and yeast Rnh201,
human RNASEH2B and yeast Rnh202, human RNASEH2C
and yeast Rnh203 enzymes [5]. Therefore, several of AGS
mutants found in human RNASEH2A, 2B, and 2C occur in
conserved regions with the yeast RNase H2 proteins and it
is possible to study their efect on genomic stability using
yeast. For example, rnh201 G42S corresponds to an AGS
mutation in humans.
The RNH201 subunit in yeast harbors the catalytic site
of RNase H2, so mutations in this gene are expected to
negatively afect enzymatic activity due to distortion of
this site [8]. Proliferating cell nuclear antigen (PCNA) is a
DNA clamp that is vital to DNA replication and repair, and
in addition, improves RNase H2s function by serving as a
clamp between the enzyme and DNA strand during ribo-
nucleotide extraction [9]. The PCNA-interacting-peptide-
box (PIP-box) encodes this PCNA interaction with RNase
H2 and is located on the RNH202 subunit, therefore a mu-
tation would impede PCNA binding [10]. rnh203 K46W,
a mutation in the RNH203 subunit, has also been found to
be correlated with AGS in the corresponding human gene,
RNASEH2C [11].
RNase H2 dependency on DNA repair in vivo
RNase H2 has largely been studied in vitro, and therefore
studies are needed to demonstrate in vivo how mutating
or overexpressing the enzyme will afect the DNA repair
process. The efects of mutated and overexpressed RNase
H2 on cell viability in the presence of DNA damaging
agents, such as hydroxyurea, methyl methanosulfate, and
phleomycin, has yet to be studied. RNase H1 is another
enzyme involved in ribonucleotide extraction, however
this enzyme has been observed only to remove stretches
of four ribonucleotides or more [12]. Further investigation
is needed in the presence and absence of RNase H1, to see
whether the function of this enzyme will be altered in the
absence or overexpression of its counterpart, RNase H2.
Additionally, RNase H2 has largely been studied in vitro,
and therefore further work is required to demonstrate in
vivo how mutating or over-expressing the enzyme will af-
fect the DNA repair process.
Conclusions
Ribonucleotide excision repair is a vital mechanism that
occurs in the nucleus of every cell; consequently the cur-
rent knowledge about this intricate process needs to be
expanded to develop cures for several diseases that pro-
liferate society today. In order to beter understand AGS,
and lupus and congenital HIV disorders accordingly, it
is highly important to illustrate the efects of altering the
natural state of RNase H2 in vivo. With this information,
PERSPECTIVE
the mechanism of RNase H2 can then be illuminated, re-
sulting in treatment possibilities after further research is
performed in the future.
References
1. Nick McElhinny S., Kumar D., Clark A., Wat D., Wats B., Lund-
strm E., Johansson E., Chabes, A. Kunkel T. Genome instability
due to ribonucleotide incorporation into DNA. Nature Chem Biol.
2010;6:774-781
2. Nick McElhinny S., Wats B., Kumar D., Wat D., Lundstrm E.,
Burgers P., Johansson E., Chabes A., Kunkel T. Abundant ribonu-
cleotide incorporation into DNA by yeast replicative polymerases.
Proc. Natl. Acad. Sci. USA 2010;107:4949-4954
3. Egli M., Usman N., Rich A. Conformational infuence of the ribose
20-hydroxyl group: crystal structures of DNA-RNA chimeric du-
plexes. Biochem. 1993;32;3221-3237
4. Dickerson R. E., et al. The anatomy of A-, B-, and Z-DNA. Science.
1982;216:475
5. Crow Y., Leitch A., Hayward B., Garner A., Parmar R., Grifth E.,
Ali M., Semple C., Aicardi J., Babul-Hirji R., et al. Mutations in
genes encoding ribonuclease H2 subunits cause Aicardi- Goutires
syndrome and mimic congenital viral brain infection. Nat. Genet.
2006;38:910-916
6. Rice G., Patrick T., Parmar R., Taylor C., Aeby A., Aicardi J., Ar-
tuch R., Montalto S., Bacino C., Barroso B., et al. Clinical and mo-
lecular phenotype of Aicardi-Goutieres syndrome. Am. J. Hum.
Genet.2007;81:713-725
7. Rice G. I., et al. (2009) Mutations involved in Aicardi-Goutires
syndrome implicate SAMHD1 as regulator of the innate immune
response. Nat.Genet. 41:829832
8. Jeong H., Backlund P., Chen H., Karavanov A., Crouch R. RNase
H2 of Sacchromyces cerevisiae is a complex of three proteins. Nu-
cleic Acids Res. 2004;32:407-414
9. Bubeck D., Reijna M., Graham S., Astell K., Jones E., Jackson A.
PCNA directs type 2 RNase H activity on DNA replication and
repair substrates. Nuc. Acids Res. 2011;39:3652-3666.
10. Chon H., Vassilev A., DePamphilis M., Zhao Y., Zhang J., Burgers
P., Crouch R., Cerritelli S. Contributions of the two accessory sub-
units, RNASEH2B and RNASEH2C, to the activity and properties
of the human RNase H2 complex. Nuc. Acids Res. 2009;37:96-110
11. Rohman M., Koga Y., Takano K., Chon H., Crouch R., Kanaya S.
Efect of the disease-causing mutations identifed in human ribo-
nuclease (RNase) H2 on the activities and stabilities of yeast RNase
H2 and archaeal RNase HII. FEBS J. 2008;275:4836-4849
12. Cerritelli, S. M., and Crouch R. J. Ribonuclease H: the enzymes in
eukaryotes. FEBS J. 2009;276:1494-1505.
PERSPECTIVE
GTTOWER.ORG | 29
PERSPECTIVE
LaDeidra Monet Roberts
1
& Manu Platt, PhD
1
I mpl i cat i ons of hi ghl y act i ve
ant i r et r ovi r al t her apy i n t he
devel opment of car di ovas cul ar
di s eas e i n HI V pat i ent s
Since the identifcation of HIV in 1983, the dis-
ease has afected millions worldwide. Highly
active antiretroviral therapies (HAART) were
implemented as standard treatment for the
virus to target diferent stages of the HIV life
cycle to suppress viral replication. Major ad-
vances in HAART have contributed to longer
life expectancies of people living with HIV.
Palella et al. showed signifcant declining rates
in morbidity and mortality in infected patients
and suggested proportional response of decline
was shown with increasing potency or more an-
ti-HIV drugs used in the treatment. Specifcal-
ly, this showed that combination therapy was
more benefcial than monotherapy, suggesting
that it should become the standard treatment in
HIV+ patients.
Over the years, negative side efects have
been associated with HAART, such as meta-
bolic disorders lead to the development of co-
morbidities that decrease the quality of life of
patients. Although combination HAART regi-
mens are atributed to improvements in sup-
pressing HIV viral replication and slowing
progression to AIDS, prevalent studies have
1
Wallace H. Coulter Department of Biomedical Engineering, College of Engineering, Georgia Institute of Technology.
Correspondence should be addressed to LR (lroberts30@gatech.edu).
Major advances in highly active antiretrovi-
ral therapies (HAART) have contributed to
longer life expectancies of people living with
HIV. Palella et al (1998) studied the changes in
mortality rates as well as incidence of oppor-
tunistic infections in patients who received
antiretroviral therapy (Palella et al., 1998).
Results showed signifcant declining rates in
morbidity and mortality in infected patients
who were exposed to more potent treatment.
They also found that combination therapy
was more benefcial than monotherapy, sug-
gesting that it should become the standard
treatment in HIV+ patients. Although major
advances in HAART have prolonged the life
expectancies of HIV+ patients, this perspec-
tive delves deep into how HAART might be
contributing to the co-morbidity of cardiovas-
cular disease in HIV+ patients.
suggested that long-term exposure to these treatments
may increase progression of cardiovascular disease (CVD)
in infected patients (Friis-Moller et al., 2003; Vitecoq et
al., 2003). The multi-factorial complications of the devel-
opment of CVD in HIV patients are not fully elucidated,
but an assessment of culminating research could provide
some insight on future investigational avenues to rectify
this issue.
Cardiovascular implications with HAART treatment
One of the frst studies that observed cardiovascular com-
plications in the presence of HAART treatment showed
a 26% relative increase in the rate of myocardial infarc-
tions possibly associated with combination antiretroviral
therapy (Friis-Moller et al., 2003). During follow up stud-
ies, risk factors, such as hypertension, diabetes, and lipo-
dystrophy, were atributed to discrepancies in cholesterol
and triglyceride levels compared to baseline. From these
results, antiretroviral therapy was suggested to cause ad-
verse metabolic side efects, thereby possibly leading to
cardiovascular complications (Friis-Moller et al., 2003).
Since it was unclear about a direct correlation between an-
tiretroviral therapy and myocardial infarctions at the time,
it was believed that the benefts of these antiretroviral
drugs outweighed the risks (Friis-Moller et al., 2003). Fur-
ther, Vitecoq et al. found that incidence of coronary heart
disease (CHD) was higher in HIV-infected patients than
originally expected based of of previous studies showing
that regimens including protease inhibitors contributed to
vascular complications in patients (Vitecoq et al., 2003).
Atherosclerosis in HIV+ patients
Since the association of CVD risk and antiretroviral expo-
sure, current research has been devoted to understanding
the pathophysiology of atherosclerosis and its exacerba-
tion in HIV+ patients. Cellular components have been
studied to provide insight on the development of car-
diovascular complications. Specifcally, the candidates
of interest have been the endothelium and monocytes
because of their involvement in oxidizing and ingest-
ing low density lipoprotein (LDL), which contrib-
utes highly to atherosclerosis (Kadar & Glasz, 2001;
Kline & Sutlif, 2008). Further, studies have implicated the
virus in combination with HAART contribute to endothe-
lial dysfunction in HIV+ people which might pose prob-
lematic to the cardiovascular health of infected patients
(Kline & Sutlif, 2008).
Extracellular matrix degradation
Much progress in research has revolutionized awareness
in CVD in HIV patients, but few studies in the past have
examined the specifc molecular mechanisms of HAART
in the increased risk of cardiovascular disease in HIV+
patients. Degradation of the extracellular matrix (ECM)
within arteries, a key factor in atherogenesis and arterial
stifening, is characteristic in cardiovascular disorders.
This remodeling has been associated with cysteine prote-
ases called cathepsins, specifcally K, L, S, V, potent colla-
genases and elastases in the body that have been shown to
be upregulated in atherosclerotic plaques in CVD (Garcia-
Touchard et al., 2005; Liu et al., 2006).
Cathepsin L
Other studies have shown that cathepsin L played a sig-
nifcant role in atherogenic conditions using immunohis-
tochemistry and in vitro studies with smooth muscle cells,
endothelial cells, and monocyte-derived macrophages
found in atheroma lesions. Patient serum also showed that
those with coronary artery stenosis had higher cathepsin L
levels (Liu et al., 2006). Hansen et al. showed that a com-
mon HAART protease inhibitor azidothymidine (AZT)
promotes arterial remodeling by increasing the proteolytic
activity of cathepsins in mouse arteries, thereby support-
ing that cathepsin activity should be further studied in as-
sociation with this disease (Hansen et al., 2013).
Immuno-infammatory responses
Since these proteases have been shown to play a role in ar-
terial remodeling in CVD, then they should be studied fur-
ther in specifc cell types found within the arteries. Infam-
mation involves endothelial cell-monocyte interaction as
well as infammatory cytokines that activate cell adhesion
molecules to promote monocyte transendothelial migra-
tion (Keegan, Wilder, & Plat, 2012), the mechanistic way
PERSPECTIVE
GTTOWER.ORG | 31
that this contributes to proteolysis and vascular remodel-
ing in atherosclerosis would be useful to study. Keegan
et al. showed that increases in cathepsin S and V activity
were atributed to key phosphorylation of the Jun N-ter-
minal kinase linked intracellular pathways of infamma-
tory cytokine TNF, which induces monocytes to bind to
the endothelium in the infammatory response in the vas-
culature (Keegan et al., 2012). This study provided insight
on monocytes being a useful cell type to study in regards
to arterial remodeling because of its role in the infamma-
tory response and interaction with the endothelium of the
artery as well as molecular mechanisms that elucidated a
specifc pathway that cathepsins play an important role in
remodeling in the early stages of arterial remodeling seen
in CVD.
Because of the intrinsic infammation caused by the
HIV virus, atherogenesis is more likely to occur and is
driven by infected macrophages (Crowe et al., 2010). Pre-
cursors to macrophages, monocytes are known to secrete
cathepsins as well as play a role in the initial stages of the
immune response. However, HIV infection causes them
to not function properly as an immune agent, which sup-
ports that they are a sufcient cell type to study in regards
to CVD in HIV patients. Since antiretroviral drugs target
the HIV virus, these drugs might also have an efect on
proteolytic activity in monocytes and macrophages that
might further alter their function as well, which would be
interesting in future studies.
Future research implications
Prolifc research has studied the development of CVD
in the presence of HAART in HIV patients. However, a
gap remains on how these drugs contribute on a molecu-
lar level to cellular interactions that ultimately lead to the
macroscopic complications seen in clinical setings. Study-
ing the efects of HAART on monocytes/macrophages
could provide insight on the changes in cathepsin activity
and the mechanisms that are physiologically relevant in
contributing to the exacerbation of plaque in the system,
and ultimately, lead to therapeutic targets to mitigate car-
diovascular complications in HIV+ patients and increase
their quality of life.
References
1. Crowe, S. M., Westhorpe, C. L., Mukhamedova, N., Jaworowski,
A., Sviridov, D., & Bukrinsky, M. (2010). The macrophage: the
intersection between HIV infection and atherosclerosis. J Leukoc
Biol, 87(4), 589-598. doi: 10.1189/jlb.0809580
2. Friis-Moller, N., Sabin, C. A., Weber, R., dArminio Monforte, A.,
El-Sadr, W. M., Reiss, P., . . Lundgren, J. D. (2003). Combination
antiretroviral therapy and the risk of myocardial infarction. N Engl
J Med, 349(21), 1993-2003. doi: 10.1056/NEJMoa030218349/21/1993
[pii]
3. Garcia-Touchard, A., Henry, T. D., Sangiorgi, G., Spagnoli, L. G.,
Mauriello, A., Conover, C., & Schwart, R. S. (2005). Extracellular
proteases in atherosclerosis and restenosis. Arterioscler Thromb
Vasc Biol, 25(6), 1119-1127. doi: 10.1161/01.ATV.0000164311.48592.
da
4. Hansen, L., Parker, I., Monet Roberts, L., Sutlif, R. L., Plat, M. O.,
& Gleason, R. L., Jr. (2013). Azidothymidine (AZT) leads to arterial
stifening and intima-media thickening in mice. J Biomech, 46(9),
1540-1547. doi: 10.1016/j.jbiomech.2013.03.021
5. Kadar, A., & Glasz, T. (2001). Development of atherosclero-
sis and plaque biology. Cardiovasc Surg, 9(2), 109-121. doi:
S0967210900000971 [pii]
6. Keegan, P. M., Wilder, C. L., & Plat, M. O. (2012). Tumor necrosis
factor alpha stimulates cathepsin K and V activity via juxtacrine
monocyte-endothelial cell signaling and JNK activation. Mol Cell
Biochem, 367(1-2), 65-72. doi: 10.1007/s11010-012-1320-0
7. Kline, E. R., & Sutlif, R. L. (2008). The roles of HIV-1 proteins and
antiretroviral drug therapy in HIV-1-associated endothelial dys-
function. J Investig Med, 56(5), 752-769. doi: 10.1097/JIM.0b013e31
81788d1500042871-200806000-00004 [pii]
8. Liu, J., Sukhova, G. K., Yang, J. T., Sun, J., Ma, L., Ren, A., . . . Shi, G.
P. (2006). Cathepsin L expression and regulation in human abdom-
inal aortic aneurysm, atherosclerosis, and vascular cells. Athero-
sclerosis, 184(2), 302-311. doi: 10.1016/j.atherosclerosis.2005.05.012
9. Vitecoq, D., Escaut, L., Chironi, G., Teicher, E., Monsuez, J. J.,
Andrejak, M., & Simon, A. (2003). Coronary heart disease in HIV-
infected patients in the highly active antiretroviral treatment era.
AIDS, 17 Suppl 1, S70-76
PERSPECTIVE
Thuy Le
1
& Athanassios Sambanis, PhD
2,3
Del i neat i on of cel l - bas ed t her api es
t o t r eat i ns ul i n- dependent di abet es
Diabetes, a metabolic disease that is character-
ized by high, uncontrolled blood glucose, re-
sults from one of two ways: the pancreas not
producing enough insulin to maintain normal
blood glucose levels or the bodys cells not re-
sponding to the insulin that is produced. This
disease is a major health problem that afects
approximately 23.6 million people in the United
States, 27% of which (about 6.4 million people)
are insulin-dependent (CDC, 2007). Without
proper regulation, high blood glucose increases
risk for heart disease, kidney failure, blindness,
and nerve damage (CDC, 2007).
The most common treatment for insulin-de-
pendent diabetes (IDD) patients involves self-
monitoring their blood glucose level several
times a day and self-injecting their bodies with
insulin. This method does not continuously
monitor blood glucose levels and thus, excur-
sions from normoglycemia often occur without
the patients knowledge. Current research fo-
cuses on developing a treatment method that
works within the body of IDD patients and
1
2
School of Chemical & Biomolecular Engineering, College of Engineering, Georgia Institute of Technology.
3
Parker H.
Petit Institute for Bioengineering & Bioscience. Correspondence should be addressed to TL (thuy7@gatech.edu).
In 2007, according to the Center for Disease
Control and Preventation, about 6.4 million
people in the United States sufer from insu-
lin-dependent diabetes. Current treatment for
this metabolic disease relies on constant self-
monitoring from the patients. Researchers
are continuously fnding ways to improve the
cell-based model in order to produce a bioarti-
fcial pancreas. These bioartifcial pancreases
are made by encapsulating insulin-producing
cells in a semi-permeable barrier to mimic the
endocrine functions of a non-diseased pan-
creas. This paper will review the progession
of improvements made to the encapsulation
barrier in order to accomplish the bioartifcial
pancreas. It will also describe the ongoing ef-
forts of the Sambanis Lab on Georgia Techs
campus to beter develop a treatment for
insulin-dependent diabetes. This treatment
method could increase the quality of life and
potentially cure insulin-dependent diabetes
for millions of patients in the United States.
PERSPECTIVE
GTTOWER.ORG | 33
freely senses the amount the of glucose in the blood
as well as administers an appropriate amount of insulin
needed to regulate glycemic levels. This paper describes
the ongoing work of the Sambanis Lab on Georgia Techs
campus to develop a beter treatment for IDD.
Bioartifcial pancreas
Although the current treatment method regulates blood
glucose, it does not compare to the glycemic regulation
found in a non-diseased state (Sambanis, 2011). Research
in the Sambanis Lab examines the possibility of other
treatments for IDD, with a focus on the use of cell-based
therapies. Cell-based insulin delivery remains a promising
approach to alleviate glycemic monitoring and to provide
more physiologic insulin delivery for insulin dependent
diabetes (IDD). Successful treatment will not only reduce
the patients regular monitoring, but improve glycemic
control, which would reduce long-term complications as-
sociated with diabetes.
Researchers are currently investigating methods to
produce a bioartifcial pancreas which secretes insulin in
response to physiologic cues. The bioartifcial pancreas is
made by encapsulating insulin-producing cells, most com-
monly islets, in a semi-permeable hydrogel barrier, allow-
ing the delivery of insulin to IDD patients while simul-
taneously protecting the cells after transplantation. These
bioartifcial pancreases often require co-administeration
with immunosuppressants to reduce the immunogenicity
of the implanted cells. This reduces the immune response
and helps to decrease the rejection rates of the bioartifcial
pancreas by the patients. Although immunosuppression
protocols are necessary, long-term doses expose the pa-
tients to greater risks of developing an immune defency
disease as well as reduce islet function and viability and
therefore need to be modifed (Paty, 2002).
Hydrogels for cell microencapsulation
Schmidt (2008) reviews the current hydrogels utilized for
cell-based therapies. A successful hydrogel depends on
the cell encapsulation process, the level of immunogenic-
ity of the cells, difusion of insulin within the material, and
long-term structural stability of hydrogel. These hydrogel
properties are improved by making modifcations to the
chemical structure and the gelled microstructure. Previ-
ous studies have tested a various range of chemical struc-
tures for the encapsulation gel, but the primary encapsula-
tion system utilized alginate microcapsules (King, 2011).
One problem with the alginate beads is that they allow
large molecules like Immunoglobulin G (IgG) to perme-
ate through. IgG is a molecule that activates a cascade of
immune protein production to eliminate foreign bodies,
which kills the cells inside the beads.
Microcapsule surface coatings
To defend against IgG permeation, other studies have
found that coating the alginate beads with a poly (l-lysine)
[PLL] layer will allow the beads to retain the successful
properties of the alginate layer, but will also prevent IgG
penetration through the beads. The most important aspect
of the PLL layer is its resistance to IgG to reduce possible
atacks on the beads. However, the chemistry of the PLL
causes an infammatory reaction that is not desired for
treatment. The PLL layer atracts cellular adhesion on the
surface of the capsule, which leads to poor performance
of the beads (King, 2001). One goal for researchers now is
to fnd another material to cover the PLL layer with. They
want a material that will not only preserve the successful
properties of the alginate and PLL layer, but also protect
against an infammatory response.
Alginate-PLL-Alginate microcapsules
Currently the A-PLL beads are covered with an outer lay-
er of alginate, in an A-PLL-A sequence. When researchers
added a thin layer of alginate, the beads encapsulating xe-
nogeneic islets were rejected. When a thick layer of algi-
nate was added, the beads became too big and the amount
of islets that could be transplanted was decreased. For ex-
ample, compared to the smaller beads, instead of ten beads
in a dose, the size of beads would only allow four beads
in one dose. However, in both cases, these beads were un-
appealing because they were infamed and still elicited a
fbrotic response (Clayton, 1993).
PERSPECTIVE
Alginate-PLL-PEG microcapsules
Sawhney (1993) introduced a procedure to add a poly
(ethylene glycol)-based hydrogel upon the alginate-PLL
beads. Poly (ethylene glycol) or PEG covalently bonds to
the PLL layer of the hydrogel enhancing the gels stabil-
ity by essentially forming a shell around the beads. The
PEG layer does not block the insulin from difusing out,
does not nearly atract cell adhesion as much as the A-PLL
beads, and maintains the PLL layers ability to resist IgG
permeation. The problem with the procedure in Sawhney
(1993) is that it required a lot of specialized equipment and
expensive reagents. Researchers are looking for a method
that is easily applied without specialized equipment and
can be used on a large scale (i.e. is not expensive).
The Sambanis Lab on Georgia Techs campus has been
developing and characterizing a PEG coating for alginate-
PLL capsules. In order to evaluate the potential of utilizing
this PEG coating, four assays were employed: cytotoxicity,
stability, difusivity, and permeability. To demonstrate
that the PEG layer does not adversely afect the favorable
characteristics of the alginate microcapsules, the capsules
were tested in vitro: by themselves, and when they contain
encapsulated cells. If results of all four assays show that
this PEG chemistry is suitable for cell-encapsulation, the
beads will then be tested in vivo with a mouse model be-
fore implantation in humans.
Implications
The cell-encapsulation research has the potential to rede-
fne treatment for IDD. Artifcial pancreases could regu-
late the glycemic levels of IDD patients to where it will
be comparable to that of a non-diseased patient. The cells
will be able to sense the level of glucose in the bloodstream
and automatically administer a dose of insulin, if needed,
to normalize the glycemic levels. Patients will no longer
have to bother with constant monitoring and frequent
injections. Furthermore, their risks of diseases that occur
from long-term irregular glycemic balance, such as heart
disease and kidney failure, will be reduced (CDC, 2007).
Looking forward
Artifcial pancreas research has possibly found a highly
suitable hydrogel for IDD treatment. In order to concrete-
ly introduce this cell-encapsulation method for humans,
more research is necessary to validate the potential appli-
cation of encapsulated cells for the treatment of IDD. If
successful, this method would increase the quality of life
for the millions of people sufering from IDD worldwide.
References
1. C.D.C. (2007). National Diabetes Fact Sheet, 2007.
2. Sambanis, A. (2011). Artifcial Organs | Pancreas. 5, 699711. doi:
10.1016/B978-0-08-088504-9.00418-9
3. Paty, B. W., Harmon, J. S., Marsh, C. L., & Robertson, R. P. (2002).
Inhibitory efects of immunosuppressive drugs on insulin secre-
tion from HIT-T15 cells and Wistar rat islets. Transplantation, 73,
353-357.
4. Schmidt, J. J., Rowley, J., & Kong, H. J. (2008). Hydrogels used for
cell-based drug delivery. Journal of Biomedical Materials Research
Part A, 87A(4), 1113-1122. doi: 10.1002/jbm.a.32287
5. King, A. (2001). Evaluation of Alginate Microcapsules for Use in
Transplantation of Islets of Langerhans. Acta Universitatis Upsa-
liensis. Comprehensive Summaries of Uppsala Dissertations from
the Faculty of Medicine 1072. 43 pp. Uppsala. ISBN 91-554-5113-6
6. Clayton, H. A., James, R. F. L., & London, N. J. M. (1993). Islet mi-
croencapsulation: a review. Acta Diabetol, 30, 181-189.
7. Sawhney, A. S., Pathak, C. P., & Hubbell, J. A. (1993). Interfacial
photopolymerization of poly(ethylene glycol)-based hydrogels
upon alginate-poly(l-lysine) microcapsules for enhanced biocom-
patibility. Biomaterials, 14(13), 1008-1016.
PERSPECTIVE
GTTOWER.ORG | 35
Harrison Bartlett
1
& Lena H. Ting, PhD
1,2
Robot i c exos kel et ons and t he
chal l enges f aci ng t he f i el d
Robotic exoskeletons are robots that can be
worn by users to move with the body for vari-
ous purposes such as rehabilitation or strength
augmentation. Exoskeletons have been created
to work in conjunction with multiple parts of
the human body, but primarily focus on the
legs, arms, and hands. Many exoskeletons have
been produced in both academic and industrial
setings to various levels of success. Only by
examining previous approaches to exoskeleton
design and the problems associated with these
robots, can new efective designs be generated.
By examining previous work in the feld, past
successes can be built upon and failures can be
overcome to produce new robotic exoskeletons
that are able to improve the lives of their us-
ers.
Robotic exoskeletons that have been de-
signed in the past have difered vastly in their
approaches to actuator technology, power sup-
plies, mechanical design, control, and perfor-
mance evaluation. Each of these design deci-
sions provides challenges to the future design
of exoskeletons. These challenges include the
weight of the system, power supply, actuation,
human machine interface/control, and device
performance evaluation.
1
2
George W. Woodruf School of Mechanical Engineering, College of Engineering, Georgia Institute of Technology.
Correspondence should be addressed to HB (hbartlet3@gatech.edu).
Robotic exoskeletons have been built for aug-
menting human performance, assisting with
disabilities, studying human physiology, and
re-training motor defciencies. The purpose of
this paper is to review recent developments in
robotic exoskeletons and challenges current-
ly facing the feld. We review the four broad
categories of robotic exoskeletons: rehabili-
tative, assistive, augmenting, and haptic. Ad-
ditionally, we comment on several challeng-
esincluding system weight, power supply,
actuation, human machine interface/control,
and device performance evaluationwhich
require further investigation in order to meet
design goals.
PERSPECTIVE
Current robotic exoskeletons
There are multiple categories of robotic exoskeletons, each
with diferent design requirements and target populations
based on their functional goals. These categories include
rehabilitative, assistive, augmenting, and haptic exoskel-
etons.
Rehabilitative robots
Rehabilitative robots are used to guide the user through a
series of rehabilitative motions to aid in recovery from an
injury or to regain motor skills. These robots can be used
in temporary rehabilitative training programs to improve
the motor function of a patient. These devices can be used
in conjunction with virtual reality or video games to give
the user feedback and to help the user to stay focused on
his or her rehabilitation. Most of these exoskeletons are
fxed to a stationary structure such as a wall or a chair (Van
Asseldonk 2008; Gupta 2007). By anchoring the device to
an immobile object, the issue of heavy system weight may
be avoided by rehabilitative robots.
Assistive exoskeletons
Assistive exoskeletons work with physically impaired us-
ers to assist the users movements. These devices are de-
signed to work with paraplegics or those with functional
weakness to provide the user the ability to move normally
and could be used permanently or until the user has re-
gained sufcient motor function (Kiguchi 2007; Neuhaus
2011; Perry 2007; Quintero 2011). These devices difer from
rehabilitative robots in that they are intended to help users
perform everyday movements instead of executing prede-
termined rehabilitative exercises/games.
Augmenting exoskeletons
Augmenting exoskeletons work with the user to enhance
his or her strength; these devices have been typically used
for heavy lifting applications such as factory foor lifting
or military applications and are almost always portable
or atached to a tether to provide power to the system
(Kazerooni 2005; Prat 2004; Walsh 2007; Liu 2004).
The primary users of these devices are able-bodied
individuals performing tasks that require extraor-
dinary strength or stamina.
Haptic exoskeletons
Haptic exoskeletons have been used to interact with vir-
tual environments or to control robotic manipulators with
haptic (tactile) feedback (Dovat 2008; Letier 2008). These
robotic devices exert forces on the body as the user inter-
acts with a virtual environment. In this way, objects in the
virtual environment can be felt and manipulated. These
robots can also be used as part of a master-slave system
in which the robotic exoskeleton master controls a ro-
botic slave in another location (Letier 2008).
Challenges facing the feld
Weight of the system
The weight of a robotic systems components often limits
the capabilities of the device (Cenciarini 2011). Heavy com-
ponents such as the actuators and power supply demand
more power from the power source and limit the portabil-
ity of the exoskeleton. To tackle this problem, some groups
have chosen to anchor their device to an immobile object
(Perry 2007; Cavallaro 2006). In this case, the user does
not have to support the weight of the robot and the power
source does not have to be carried by the robot. This strat-
egy is more common in rehabilitative exoskeletons. Some
groups have chosen to detach the heavy components of
the exoskeleton such as the power supply and carry these
heavy components along separately from the exoskel-
eton (Kong 2006; Kiguchi 2007). Others have reduced the
weight of the exoskeleton by utilizing a more passive ap-
proach to actuation; these robots employ the use of springs
and other energy-storing devices (Walsh 2006; Walsh 2007;
Valiente 2005; Krut 2010; Rahman 2006). Additionally, the
material choice for the exoskeleton plays a major role in
determining the mass of the robotic system. Because of the
excessive weight of some robots many groups have chosen
to construct their systems from aluminum parts, making
use of aluminums high strength-to-weight ratio (Van der
Kooij 2006; Gupta 2007).
PERSPECTIVE
GTTOWER.ORG | 37
Power supply
Current power supplies for robotic exoskeletons are often
heavy and not very efcient. Additionally, power sourc-
es are not able to provide power to exoskeletons for very
long periods of time. Power sources with short lifespans
limit the utility of a device and add considerable mass to
the system. The power source problem is one of the largest
issues facing commercially available products because the
devices cannot be used for long periods of time (Honda
Stride Management Assist, Honda Bodyweight Support
Assist, Rex Bionics, Strausser 2011, Tsukahara 2009).
Some groups have atempted to solve the problem of
portable, efcient power sources by housing their devices
within facilities (Colombo 2000). This approach allows
the exoskeleton to connect to external power via a plug
(immobile devices) or power tether (mobile devices). The
most efective commercially available devices employ the
use of rechargeable bateries to atempt to solve the pow-
er-source problem (Esquenazi 2012).
Actuation
Many diferent approaches have been atempted in terms
of actuation, however, it is unclear which method is the
most efective. There is a tremendous variation in the ap-
proaches that diferent groups have adopted for actuat-
ing their robotic systems. Most exoskeletons created in
research setings use servo motors to actuate their robots,
but the low strength-to-weight ratio of such actuators limit
their efcacy in a portable system (Liu 2004; Kong 2006).
Many commercially available augmentation exoskeletons
use hydraulic actuators to power their systems, but sys-
tems that employ hydraulic actuators have many draw-
backs such as noisy machinery, bulky actuators, and a
low payload to system weight ratio (Walsh 2006). Many
research groups have recently begun to design their exo-
skeletons with series elastic actuators (Van der Kooij 2006;
Prat 2004; Neuhaus 2011). These actuators may also fa-
cilitate human-machine interaction because they allow for
impedance control (Hogan 1984).
Human-machine interfaces
The challenges posed by the human machine interface
and the control of exoskeletons depend strongly on the
exoskeletons purpose. Additionally, the use of noisy bi-
ological signals poses signifcant problems for controller
design. There is a great deal of variation in the scientifc
community with regards to how to best control a robotic
exoskeleton interacting with a human user. User safety
and determining user intent are of utmost importance
when designing a controller for such a device. It is also
important that a controller allow for minimal training by
the user.
Some groups have implemented impedance control-
lers in their robots so that the robot can safely interact with
the human user (Van der Kooij 2006; Gupta 2007). In this
control setup, the impedance of the user is matched by the
robot to provide coordinated motion of both the robot and
user. Other exoskeletons have used position control of the
robot in order to move the users limbs through a prede-
termined trajectory. This type of control is most common
with rehabilitative exoskeletons (Colombo 2000). Other
devices have atempted to determine user intent by mea-
suring biological signals such as muscle activity (Cavalla-
ro 2006; Kiguchi 2007). Still, other leg exoskeletons atempt
to determine user intent by monitoring trunk motion or
forces exerted by the upper body (Strausser 2011; Quin-
tero 2011; Tsukahara 2009).
Device performance evaluation
There is no standard method of analyzing exoskeleton
performance currently, which causes a major problem in
terms of determining the progress being made with suc-
cessive exoskeleton designs. As new exoskeleton designs
emerge, the groups producing the robots tend to state that
there is improvement in patient mobility or that the device
is successful. However, without a standard metric of com-
parison, the efcacy of many of these robots is unknown.
One typical method of device validation that is used by
some groups is the tracking of the users joint kinematics
and comparing these kinematics to a healthy control (Van
Asseldonk 2008; Walsh 2006; Gupta 2007). Although this
method is the most common, the quantifable metrics that
are calculated from the joint kinematics difer from robot to
robot, making the comparison of exoskeleton performance
PERSPECTIVE
particularly difcult. Additionally, when evaluating the
performance of a device it is important to understand the
purpose of the robot. For example, rehabilitative robots
may need to be evaluated diferently from augmenting or
haptic exoskeletons.
Looking forward
When looking to the future of robotic exoskeletons, it is
important to note the hurdles that mark the path to a suc-
cessful device. The design of a successful robotic exoskel-
eton depends largely on its intended purpose; augment-
ing exoskeletons have drastically diferent requirements
from rehabilitative exoskeletons. With regard to future
designs, the challenges of system weight, efcient power
supplies, actuation, efective control, and performance
evaluation all need to be tackled. These problems may be
solved through the collaboration between researchers in
diferent disciplines such as materials science, electrical
engineering, rehabilitation, medicine, neuromechanics,
controls, and others. Once these design hurdles have been
overcome, efective exoskeletons may be realized for re-
habilitative, augmentative, haptic, and assistive purposes.
References
1. Cenciarini, M., & Dollar, A. M. (2011). Biomechanical consider-
ations in the design of lower limb exoskeletons. Paper presented
at the Rehabilitation Robotics (ICORR), 2011 IEEE International
Conference.
2. Cavallaro, E. E., Rosen, J., Perry, J. C., & Burns, S. (2006). Real-time
myoprocessors for a neural controlled powered exoskeleton arm.
Biomedical Engineering, IEEE Transactions on, 53(11), 2387-2396.
3. Colombo, G., Joerg, M., Schreier, R., & Diet, V. (2000). Treadmill
training of paraplegic patients using a robotic orthosis. Journal of
rehabilitation research and development, 37(6), 693-700.
4. Dovat, L., Lambercy, O., Gassert, R., Maeder, T., Milner, T., Leong,
T. C., & Burdet, E. (2008). HandCARE: a cable-actuated rehabilita-
tion system to train hand function after stroke. IEEE transactions
on neural systems and rehabilitation engineering: a publication of
the IEEE Engineering in Medicine and Biology Society, 16(6), 582-
591.
5. Esquenazi, A., Talaty, M., Packel, A., & Saulino, M. (2012). The
ReWalk Powered Exoskeleton to Restore Ambulatory Function
to Individuals with Thoracic-Level Motor-Complete Spinal
Cord Injury. American Journal of Physical Medicine & Reha-
bilitation, 91(11), 911-921.
6. Gupta, A., & OMalley, M. K. (2007). Robotic exoskeletons for up-
per extremity rehabilitation. I-Tech Education and Publishing, Vi-
enna, Austria, 371-396.
7. Hogan, N. (1984, 6-8 June 1984). Impedance Control: An Approach
to Manipulation. Paper presented at the American Control Confer-
ence, 1984.
8. Honda Bodyweight Support Assist. Retrieved 7/08/2013, 2013,
from htp://corporate.honda.com/innovation/walk-assist/
9. Honda Stride Management Assist. Retrieved 7/08/2013, 2013,
from htp://corporate.honda.com/innovation/walk-assist/
10. Kazerooni, H. (2005). Exoskeletons for human power augmenta-
tion. Paper presented at the Intelligent Robots and Systems, 2005.
(IROS 2005). 2005 IEEE/RSJ International Conference.
11. Kiguchi, K., Imada, Y., & Liyanage, M. (2007). EMG-based neuro-
fuzzy control of a 4DOF upper-limb power-assist exoskeleton.
Paper presented at the Engineering in Medicine and Biology So-
ciety, 2007. EMBS 2007. 29th Annual International Conference of
the IEEE.
12. Krut, S., Benoit, M., Dombre, E., & Pierrot, F. (2010). MoonWalker,
a lower limb exoskeleton able to sustain bodyweight using a pas-
sive force balancer. Paper presented at the Robotics and Automa-
tion (ICRA), 2010 IEEE International Conference.
13. Kong, K., & Jeon, D. (2006). Design and control of an exoskeleton
for the elderly and patients. Mechatronics, IEEE/ASME Transac-
tions, 11(4), 428-432.
14. Letier, P., Avraam, M., Veillerete, S., Horodinca, M., De Bartolo-
mei, M., Schiele, A., & Preumont, A. (2008). SAM: A 7-DOF por-
table arm exoskeleton with local joint control. Paper presented at
the Intelligent Robots and Systems, 2008. IROS 2008. IEEE/RSJ In-
ternational Conference.
15. Liu, X., & Low, K. (2004). Development and preliminary study of
the NTU lower extremity exoskeleton. Paper presented at the Cy-
bernetics and Intelligent Systems, 2004 IEEE Conference on.
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(2011). Journal of Robotics, 2011.
17. Perry, J. C., Rosen, J., & Burns, S. (2007). Upper-limb powered exo-
skeleton design. Mechatronics, IEEE/ASME Transactions on, 12(4),
408-417.
18. Prat, J. E., Krupp, B. T., Morse, C. J., & Collins, S. H. (2004). The
RoboKnee: an exoskeleton for enhancing strength and endurance
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2004. Proceedings. ICRA04. 2004 IEEE International Conference.
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implementation of a powered lower limb orthosis to aid walking in
paraplegic individuals. Paper presented at the Rehabilitation Ro-
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PERSPECTIVE
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21. Rex Bionics. Retrieved 7/08/2013, 2013, from htp://www.rexbion-
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ing of a Human Machine Interface for a mobile medical exoskele-
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of a compliantly actuated exo-skeleton for an impedance controlled
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H., Van der Helm, F. C., & van der Kooij, H. (2008). The efects on
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during zero-force control. Neural Systems and Rehabilitation En-
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27. Walsh, C. J. (2006). Biomimetic design of an under-actuated leg
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skeleton for load-carrying augmentation. International Journal of
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PERSPECTIVE
DISPATCH
The brain is an amazingly complex structure that is always
maintaining and growing new neuronal connections. Ho-
meostatic plasticity describes the ability for a neuron to
alter its properties to maintain an overall stable level of
network activity. This complex process of regulation is
thought to involve changes in receptor density, amount of
neurotransmiter release, synapse sensitivity/responsive-
ness, and levels of excitatory/inhibitory feedback (Turri-
giano and Nelson 2004). The efects of chronic bicuculline
treatment and electrical stimulation were explored by Tur-
rigiano and Nelson, in 2004. Bicuculline is a GABA
A
recep-
tor antagonist that disinhibits network activity. GABA, the
main inhibitory neurotransmiter in the mammalian brain,
regulates the amount of excitability in the system. With-
out the normal function of GABA, activity increases dras-
tically. After two days in bicuculline, neuronal cultures
undergoe a change that eventually resets activity back to
normal, pre-drug levels. Additionally, the mechanisms
used in regulating homeostatic plasticity are believed to
be diferent depending on the type of perturbation done
to the network (Turrigiano et al. 2004).
Goel and Buonomano (2013) explored the efects of
drug incubation and chronic electrical stimulation on rat
cortical brain slices. Among other interesting results, this
study showed that the administration of a GABA
A
recep-
tor antagonist and bursts of electrical stimulation at 100Hz
both induce a post treatment decrease in the frequency
of spontaneous activity events. However, activity of the
brain slices was only studied post treatment; it was not
confrmed that the two methods induced similar increases
in activity.
Deep brain stimulation (DBS) is often used in clinical
practices to treat diseases such as depression and Parkin-
sons disease. Electrodes are implanted within the brain
1
Wallace H. Coulter Department of Biomedical Engineering, College of Engineering, Georgia Institute of Technology. Correspon-
dence should be addressed to RCL (candace.law@gmail.com).
During the frst few weeks in vitro cultured neuronal
networks exhibit spontaneous bursts of action poten-
tials, even in the absence of external input. Pharmaco-
logical intervention, as well as electrical stimulation
provide a direct means for chronically elevating spon-
taneous network activity and allow the study of homeo-
static plasticity. In this study, embryonic rat cortical neu-
rons were electrically stimulated with multi-electrode
arrays (MEAs) or disinhibited using a GABA
A
receptor
antagonist. Chronic pharmacological blockade of GAB-
A
A
receptors increased culture burst frequency and after
washing out the drug a signifcant homeostatic reduction
in bursting was observed. The same increase in elevated
burst frequency was observed for electrical stimulation
with distinct homeostatic efects. These experiments
may help improve our knowledge of clinical interven-
tions where neural tissue is subject to chronic electri-
cal stimulation, as well as identify the consequences
of these therapeutic approaches.
Rachel Candace Law
1
& Steve Potter, PhD
1
Chr oni cal l y el evat i ng
bur s t i ng r es ul t s i n
di s t i nct homeos t at i c
changes of cul t ur ed
neur onal net wor k
act i vi t y
GTTOWER.ORG | 41
and controlled amounts of electrical pulses alter the pa-
tients motor or sensory functions. Despite the use of this
procedure, litle is known about its underlying mecha-
nisms. More research in the feld of neuro-electrophys-
iology will greatly beneft both doctors and patients of
disorders that could be treated using DBS. Bicuculline
treatment and electrical stimulation are often used for in-
vitro studies of epilepsy. Here, a more spontaneously ac-
tive culture is used to model an epileptic system such as
the one used by Rolston, Laxpati, Gutekunst, Poter, and
Gross (2010). The results of this study may assist in reveal-
ing the consequences of these two widely used forms of
activity manipulation. The following set of experiments
tested the hypothesis that when increasing culture activ-
ity to the same level, bicuculline treatment and electrical
stimulation will induce similar types of homoeostatic plas-
ticity.
Materials and Methods
Cell culture
Multi-electrode arrays (MEAs) (Multi-Channel Systems)
used in these experiments contain six individual wells
with nine electrodes in each; this allows the real-time re-
cording of six separate sister cultures. The electrodes are
30m wide and arranged in a 3x3 grid, 200 m apart (Fig.
1A). Prior to plating, all MEAs were sterilized, coated in
the atachment promoting polymer polyethyleneimine,
washed, and coated in the axon growth substrate laminin.
MEAs were vital to these experiments because they sup-
ported cultures for up to 3 weeks and they allowed simul-
taneous recording and electrical stimulation through the
electrodes. Day 18 embryonic rat brains were carefully
dissected to isolate only the cerebral cortices. Dissociation
was then performed by breaking down proteins using pa-
pain, and cleaving the phosphodiester links in DNA using
DNase (Poter and DeMarse 2001). Neurons and glia were
plated onto the 6-well MEAs at a density of about 3000 live
cells per L and at a volume of 12 L. Within 24 hours,
dissociated neurons began to form connections with each
other via axons and dendrites (Fig. 1B). After two weeks
in vitro, spontaneous bursting of action potentials is ob-
served in the cultures. Cultures existed in a growth me-
dium containing serum that was partially replaced every
three days. The environment was maintained at 35C, 5%
CO2, and 65% relative humidity (Poter et al. 2001) and
the MEA was covered in a Tefon lid that is permeable to
air but not fuids (Blau, Neumann, Ziegler, and Benfenati
DISPATCH
Figure 1 Dissociated neurons on a microelectrode array
24 hours after plating. These images were taken with a phase
contrast microscope at 10X zoom. (A) Electrodes are 30 m wide
and arranged in a 3x3 grid, 200 m apart; three are shown here. (B)
Within the 24 hours, many connections between neurons are made.
2009). During this experiment, three of the six wells were
experimental and the other three were kept as controls.
MEA electrophysiology
Continuous recording of extracellular action potentials
were obtained for each electrode in the MEA. Signals
were fltered, amplifed, and then recorded using an open-
source, real-time electrophysiology interfacing system
called NeuroRighter (Rolston, Gross, and Poter 2009).
All recordings were performed in an incubator under the
same conditions previously mentioned.
Drug treatment and electrical stimulation
Bicuculline at 20 M concentrations was introduced into
the cultures at 17-18 days in vitro (DIV). This remained for
24 hours until all wells (treated and control) were washed
four times. The number of culture wide spontaneous bursts
in one hour was counted in order to fnd the change in
frequency before and after bicuculline treatment.
Electrical stimulation of the network was implement-
ed using 0.75 V, biphasic, positive frst, 400 s width
pulses at 17-18 DIV and lasting for 24 hours. The
pulses followed a Poisson distribution onto random
electrodes within the experimental wells of the
MEA (Wagenaar, Madhavan, and Pine 2005). The frequen-
cy of pulses was determined by the normalized increase
in bursts that was obtained during the bicuculline experi-
ments.
Analysis and statistics
Each cultures array-wide spike detection rate (ASDR) was
ploted using custom MATLAB code. The histogram func-
tion was used to sum the number of recorded action po-
tentials that occurred in a 10ms time bin. The number of
bursts in one hour was counted and a burst frequency was
determined. A non-parametric Mann-Whitney U test was
used to compare diferences between sets of burst rates.
One goal was to show that both bicuculline and stimu-
lation increased bursting signifcantly when compared
to controls. Additionally, it was important to show that
there was no signifcant diference between normalized
bicuculline treated burst rates and electrical stimulated
burst rates. Lastly, average normalized burst rates for the
3 hours immediately following treatment were compared
between bicuculline treated and electrically stimulated
cultures.
DISPATCH
Figure 2 Array-wide spike histograms. (A) Top, Spike histogram of a 16DIV culture treated with bicuculline for 24hrs. During treatment,
burst rate was raised to 185% of its baseline level. Bursting was completely depleted following washes, but later returned. Bottom, Spike
histogram of a 16DIV sister control culture. Bin size = 1s. Washes were performed at t = 24hrs. (B) Top, Spike histogram of a 17DIV culture
receiving electrical stimulation for 24hrs. Bursting was raised to 203% of its baseline level. Bin size = 1s. Bottom, 10min portions of spike
histogram are shown before and during stimulation. Bin size = 10ms.
GTTOWER.ORG | 43
Results
When comparing spontaneous activity of the control cul-
tures and the cultures treated with bicuculline, there was
an increase in the frequency of population bursts by an
average of 458% 92% of average baseline frequency
(n=9). Immediately following washes, spontaneous popu-
lation bursting was completely diminished. One day later,
some but not all bursting returned to an average of 41%
25% of the baseline rate. This same increase in burst rate
was atempted to be applied to other cultures electrically
through the electrodes of the MEA. With the stimulation
protocol used, not every culture displayed an increase in
bursting rate. When averaged together, a 146% increase
from baseline rate was seen (n=14). These changes in ac-
tivity were evident in each cultures array-wide spike rate
histogram (Fig. 2). Because the electrically stimulated
data was not comparable to the bicuculline treated data,
three trials from each set were pulled to be analyzed sepa-
rately. The average increase of these cultures was 189%
11% during electrical stimulation, 88.5% 22% immedi-
ately following stimulation, and 162% 23% one day after
stimulation (Fig. 3A). When comparing the two methods
of increasing activity, normalized burst rates were similar
during treatment (p>0.5) and signifcantly diferent im-
mediately following washes and the ending of stimulation
(p<0.05). One day after treatment bicuculline and stimu-
lated cultures showed similar changes in burst rate (p>0.5)
(Fig. 3B).
Discussion
It was shown that a 24-hour GABA
A
receptor blockage
disinhibited the network and induced a homeostatic de-
crease in burst frequency following washing the drug out.
Because bicuculline is a GABA
A
receptor antagonist, the
observable activity depression following disinhibition by
bicuculline appears to be due to changes in receptor func-
tion. Unfortunately, electrical stimulation did not reliably
increase network activity in every trial. Of the bicuculline
treated and electrically stimulated cultures that experi-
enced comparable activity elevation, there was a signifcant
diference in the decrease of bursting following treatment.
These fndings allowed the rejection of the hypothesis that
DISPATCH
Figure 3 Comparing bicuculline treated and electrically stimulated neuronal cultures. (A) Average percent of pre-bicuculline and
pre-stimulation burst rates over time comparing bicuculline treated cultures and electrically stimulated cultures. Activity was normal-
ized to controls and then averaged. Shaded areas represent SEM. (B) Normalized average activity for 24hrs during treatment, and 3hrs or
24hrs following treatment. Electrically stimulated and bicuculline treated cultures with similar increases in burst rate were compared. A
Mann-Whitney U test determined that burst frequencies immediately following treatment were signifcantly diferent. Bars represent SEM.
*p<0.05 (Bicuculline n=3, electrical n=3)
similar homeostatic mechanisms would take place. Addi-
tionally, the results suggest that homeostatic changes are
dependent on the method of activity perturbation. More
research is needed to explain the exact mechanisms that
are at work during each type of homeostatic response.
When compared to the study by Goel and Buonomano
(2013), it is reinforced that bicuculline treatment and elec-
trical stimulation both decrease spontaneous activity fol-
lowing the intervention. However, by analyzing only those
cultures which experienced similar increases in burst rate,
the results above show that the method of hyperactivating
the culture determines the level of homeostatic response.
Future Work
In the future, this experiment can be expanded to use a
closed-loop electrical stimulation protocol. This protocol
may involve precisely matching the fring rate and burst
dynamics produced by pharmacological disinhibition
or stimulating a culture until a fxed target burst rate is
reached. These methods will allow the study of how spik-
ing paterns can be infuenced by distinct stimulation pa-
rameters. In addition, an investigation of this phenome-
non at the synapse, the junction where one neuron acts
upon another, will be benefcial in further clarifying the
results found.
Acknowledgements
I wish to thank Dr. Steve Poter, Associate Professor of Biomedical Engi-
neering and Director of the Laboratory for NeuroEngineering at Geor-
gia Tech for supporting my research for many years. Additionally, I sin-
cerely thank my mentor and graduate student advisor, Ming-fai Fong,
PhD Candidate of the Department of Physiology at Emory University
School of Medicine for all of her encouragement, guidance, and pa-
tience throughout my time in the lab. This research was primarily sup-
ported by the National Institutes of Health (NIH) Grant R01NS079757.
References
1. Blau A, Neumann T, Ziegler C, Benfenati F (2009). Replica-mould-
ed polydimethylsiloxane culture vessel lids atenuate osmotic drift
in long-term cell cultures. Journal of Biosciences 32(1): 59-69.
2. Goel, A., & Buonomano, D. V. (2013). Chronic Electrical Stimula-
tion Homeostatically Decreases Spontaneous Activity, but Para-
doxically Increases Evoked Network Activity. Journal of neuro-
physiology, 90095(310). doi:10.1152/jn.00612.2012
3. Poter, S. M., & DeMarse, T. B. (2001). A new approach to neural
cell culture for long-term studies. Journal of neuroscience meth-
ods, 110(1-2), 1724.
4. Rolston, J. D., Gross, R. E., & Poter, S. M. (2009). A low-cost mul-
tielectrode system for data acquisition enabling real-time closed-
loop processing with rapid recovery from stimulation artifacts.
Frontiers in Neuroengineering, 2(July), 117. doi:10.3389/neu-
ro.16.012.2009
5. Rolston, J. D., Laxpati, N. G., Gutekunst, C.-A., Poter, S. M., &
Gross, R. E. (2010). Spontaneous and evoked high-frequency os-
cillations in the tetanus toxin model of epilepsy. Epilepsia, 51(11),
228996. doi:10.1111/j.1528-1167.2010.02753.x
6. Turrigiano, G. G., & Nelson, S. B. (2004). Homeostatic plasticity in
the developing nervous system. Nature Reviews Neuroscience,
5(2), 97107. doi:10.1038/nrn1327
7. Wagenaar, D., Madhavan, R., & Pine, J. (2005). Controlling burst-
ing in cortical cultures with closed-loop multi-electrode stimula-
tion. Journal of Neuroscience 25(3): 680 688.
8. Wagenaar DA, Pine J, Poter SM (2006). An extremely rich reper-
toire of bursting paterns during the development of cortical cul-
tures. BMC Neuroscience 7:11.
DISPATCH
GTTOWER.ORG | 45
Georgia Tech Mason Building

www.ezgo.com

2012 E-Z-GO Division of Textron Inc. All rights reserved.
Vivian C. Lacayo
1
& Karie Davis-Nozemack, PhD
1
The ef f ect s of t he Pat i ent Pr ot ect i on and
Af f or dabl e Car e Act on s mal l and medi um-
s i zed Amer i can bus i nes s es
Introduction
On March 23, 2010, President Barack Obama signed the
Patient Protection and Afordable Care Act (PPACA)
2
, a
law that brought much needed health insurance reform
to Americans. It ofers the possibility of health insurance
to the 50 million people who currently cannot aford to
pay for healthcare.
3
While the PPACA may pave the
way to more insured Americans, the PPACA also has un-
intended consequences. This law is works in theory but is
far from a perfect solution for all American healthcare ills.
Insurance companies, hospitals, the American public, and
small and medium sized businesses must deal with many
unresolved issues now, even though the PPACA is still too
new to know its full efects on the healthcare system and
1
Ernest Scheller Jr. College of Business, Georgia Institute of Technology. Correspondence should be addressed to VL
(vlacayo3@gatech.edu).
The Patient Protection and Afordable Care Act (PPA-
CA), also known as Obamacare, is the latest reform to
the American health insurance system created in an ef-
fort to help solve the American healthcare crisis. The
PPACA was designed to bring health insurance to 50
million Americans who cannot aford health insurance
by expanding access to afordable policies and creating
a system of incentives and penalties. The PPACA also
shifts health insurance from a market-based system to
a solidarity-based system where everyone will pay for
the small number of people who are consuming most of
the healthcare in the country, making it critical to have
as many people participate in the program as possible.
While the PPACA may pave the way to more insured
Americans, the PPACA also has unintended consequenc-
es. Unfortunately, this law subjects small and medium-
sized businesses to its education problems, perverse
growth incentives and especially the lack of health care
cost controls. Its evident that the creation of this law is
a positive step for 50 million uninsured Americans, but
it still has a long journey to become the perfect solution.
This article discusses these issues and suggests solutions
to these problems.
Today, after almost a century of trying; today, after over a year of debate; today, after all the votes have
been tallied health insurance reform becomes law in the United States of America.
- President Barack Obama
1
ARTICLE
Georgia Tech Mason Building

www.ezgo.com

2012 E-Z-GO Division of Textron Inc. All rights reserved.
GTTOWER.ORG | 47
the economy.
Two major issues associated with the PPACA are its
failure to address how the rising cost of healthcare will be
controlled and a loophole in which the PPACA does not
take into account companies with 26-49 employees, which
get neither a subsidy nor a penalty relating to health insur-
ance coverage. These two issues make it harder for com-
panies to know what to do regarding the new regulations.
This article will examine the PPACAs efects on small and
medium-sized companies and propose solutions to the
lack of education regarding it, growth limitations imposed
by it, and limited cost control measures in the regulation.
Background
With such a high number of uninsured Americans and in-
creasing healthcare costs, the United States needed a new
approach to healthcare. A potential solution is contained
in the PPACA, which was shaped by the complicated is-
sues it was intended to solve. Its complex origin has led to
a complex law.
Reforming the health insurance law
There are 50 million people in the United States that have
no means of paying for their healthcare and are unin-
sured.
4
This healthcare crisis is a problem because these
50 million people seek treatment via charity or at the gov-
ernments expense.
5
This cost-shifting passes the expense
onto compensated care and/or to the government and the
rest of the population.
6
The rising cost of healthcare exac-
erbates these transferred costs.
The primary purpose of the PPACA is to change the
market based system of healthcare to a solidarity system,
where the healthy will subsidize the cost of healthcare for
the sick.
7
Everyone enrolled in the program shares the risk
of unpredictable events; the healthy will not only subsi-
dize the unpredictably sick, but also the predictably and
chronically ill.
8
The law creates a solidarity system by pre-
venting health insurance companies from banning preex-
isting conditions, a form of health status discrimination.
9
Adoption of the PPACA
The problems of the American healthcare system have
long been known but previous eforts to fx them had
fallen short.
10
Healthcare reform was an important issue
during the 2008 presidential elections, where both Hilary
Clinton and President Barack Obama suggested diferent
approaches to cover millions of uninsured Americans. Af-
ter Barack Obama won the presidency, he started working
with Congress on health care reform.
11
The reform was ofcially named the Patient Protec-
tion and Afordable Care Act, but is commonly known as
Obamacare. Before it was signed into law by President
Obama,
12
the bill went through several rounds of legisla-
tive revisions. It was frst introduced to the House Com-
mitee on Ways and Means,
13
and the House passed the bill
on October 8, 2009.
14
That same day, the bill was presented
to the Senate. It was passed two months later on December
24, 2009.
15
The PPACA then went back to the House and
was passed on March 21, 2010. The President signed the
bill two days later,
16
enacting the most signifcant govern-
ment expansion of the $2.6 trillion healthcare system since
the 1960s.
17
The PPACA is the beginning of a shift in the United
States health insurance system from a market-based sys-
tem to a solidarity-based system where the healthy subsi-
dize the sick.
18
This presents an inherent challenge because,
for the program to thrive, everyone has to be involved.
Consequently, the more Americans who participate in the
program, the more efective -it is. To achieve universal
participation, the PPACA contains penalties, incentives,
and other methods to encourage participation. These pro-
visions make the law so complex that most people dont
understand most of its rules or consequences. The law is
a grand idea, but it has many faws that need to be ad-
dressed before it becomes the ideal solution for the Ameri-
can people.
Requirements of the PPACA
Many policymakers and lawyers are still trying to under-
stand this nearly thousand-page law. Similarly, company
managers and CEOs are unaware of the way the law will
afect them or how to deal with new regulations. For regu-
lar Americans it becomes even more challenging to under-
stand their options, whether ofered by their company or
ARTICLE
through newly created market exchanges. The complexity
of the law may ultimately discourage many people from
participating.
The PPACAs success depends on geting as many
people into the health insurance system as possible.
19
To
prevent healthy people from dropping their health insur-
ance if the price of coverage rises, an individual mandate
was established to require a person/company to either
buy health insurance or pay a fne. The PPACA also bans
any annual and lifetime limits on coverage, and it extends
the coverage to dependent children up to the age of 26.
20

This paper will primarily focus on the regulation of com-
panies.
21
A small business (up to 25 employees) will have
the opportunity to get a subsidy from the government,
22

in the form of a tax credit of up to 35% or up to 50%, after
2014, for their health insurance premiums.
23
Small com-
panies also avoid any penalty if they forgo buying health
insurance for their employees.
24
Mid-size companies get
no subsidy and no penalties in regards to health insurance
for their employees. Large companies, with 50 or more
employees, dont get any type of subsidy from the govern-
ment.
25
They do, however, face a penalty for not complying
with the law. There are two types of penalties. Failing to
ofer coverage results in a fne of $2,000 for each full-time
equivalent employee after the frst 30 employees.
26
For
large companies poor coverage will result in a $3,000 fne
for any employee geting a government subsidy to help
pay for their insurance and $2,000 fne for employees with
no government subsidy.
27
Medium companies have nei-
ther penalty for nonexistent or insufcient coverage nor
any subsidy to help cover their employees health insur-
ance premiums. The law defnes a full time employee to
be one who works 30 hours or more a week.
28
Previously,
the Fair Labor Standards Act left the distinction between
full-time and part-time employees to the discretion of the
employer.
29
The subsidies and penalties created by the
PPACA are enforced through the tax code.
Issues afecting small & medium-sized businesses
For small and medium-sized businesses, there are
three primary problems with the PPACA. The frst
lies in the lack of nonbiased educational informa-
tion available to the public. Second, the laws structure
creates limits on growth for small and medium sized busi-
nesses. The third problem is the absence of cost control
limitations for the rising costs associated with healthcare.
Education problems
Theres a lack of easy-to-understand information avail-
able to the public. After the (2012 presidential/2010 mid-
term) election that caused this law to become infamous,
there was a plethora of misinformation out for the public
to read. Much of the politically-motivated misinformation
describes the law in a very biased way that simply cre-
ates more confusion on what the new law actually entails
and who will be afected. Through the lens of politicized
information, the American public views the PPACA to be
either the best possible solution to United States health
care problems, or the worst possible solution, with people
focusing only on the negative efects of the law.
Despite how much information is available on the
PPACA, the fact that the law is so extensive and politi-
cally charged, makes it very hard for people who want to
get educated on the subject to get access to reliable and
impartial information. Many low income Americans, who
are crucial to making the law function, are also largely un-
aware of the fact that they will be eligible for subsidies or
what that entails.
30
The fact that people are uninformed
about what is happening and dont know when the dif-
ferent provisions are coming into efect,
31
combined with
the fact that the law is rolling out so fast may create low
enrollment, which may mean higher premiums for those
enrolled.
Many states have opposed certain provisions of the
PPACA and have been reluctant to promote the new law
in a nonbiased way to educate the people on their choic-
es. Some states have opposed the PPACAs expansion of
Medicaid because they believe it would be more costly for
each state in the future.
32
To be eligible to receive funding
from Congress, states have to contribute money towards
the expansion.
33
More acceptance of and participation in
the PPACA by the state governments is required to help
persuade more people to enroll.
In addition to the fact that much of the available infor-
ARTICLE
GTTOWER.ORG | 49
mation is full of political stigma, there is still a lack of gen-
eral and understandable information available to regular
Americans. Most information is intended to help insurance
companies and small businesses (websites like sga.gov),
but not the public. When information is available, its often
too complex or broad to understand. The litle information
available that is simplifed is often from companies with
hidden agendas.
34
Also, major regulation for companies
was issued at the end of December 2012.
35
Unfortunately,
the public was so focused on the holidays and the fs-
cal clif debate that people didnt notice that this crucial
regulation will afect all businesses because the number
of employees that companies have during 2013 will afect
their penalties for 2014.
36
Many businesses are unaware of
this rule because they erroneously believe that the law will
not take into account actions or decisions taken this year
because the law comes into efect in 2014.
37
Many busi-
nesses are not worried because they incorrectly think that
they have a year to plan for the PPACAs implementation,
when the fact is that the time to act has already passed.
38

This may be happening because much of the information
out there is targeted to the legal community, because the
law will be enforced through the tax code.
Growth limitations
In addition to education issues, small and medium sized
business also face perverse growth limitations under the
law. Companies with 25 or less employees receive a gov-
ernment subsidy to help them pay for health insurance
and will receive no penalty for failing to ofer health insur-
ance.
39
Companies with 26-49 employees receive no subsi-
dy for their premiums and no penalty for lack of coverage
or insufcient coverage.
40
Companies with 50 or more em-
ployees receive no subsidy for their insurance premiums,
but are subject to a penalty for lack of coverage or insuf-
fcient coverage.
41
The number of full-time workers that a company has
can dramatically afect the cost of health insurance to the
employer, thus it may signifcantly afect whether health
insurance is ofered to their employees. Small companies
(25 or fewer employees) can receive a government subsidy
up to 50% of the employers premium contribution
42
but
as soon as they hire the 26th employee, all the subsidy dis-
appears. Companies will look for ways to maintain their
subsidy since many will not be able to aford to pay for
healthcare coverage without this subsidy, which could
lead companies to artifcially limit growth to avoid the
loss of the subsidy. On the other hand, companies with
26 to 49 employees will have no incentive to start ofering
healthcare to its employees because medium-sized com-
panies are not covered at all in the PPACA. They have no
incentive or penalty to worry about. The problem is that
as soon as they reach 50 employees, they must ofer health
insurance or they will be forced to pay the penalty. Many
companies may not be ready to absorb the costs of either
the penalty or the health insurance and may choose to stop
hiring and growing.
The recent tax increases on personal income from 35%
to 39.6% will make it even more difcult for small business-
es to deal with the PPACA.
43
Because this law is enforced
through the tax code, this change will afect any small
business owner who reports their companys profts as
personal income.
44
Small business owners such as Tom
Campanaro, president and CEO of Total Gym, have halted
planned expansions due to the tax increase.
45
A companys
business structure will also infuence how it deals with the
new law, since the income of many corporations are sub-
ject to double taxation at both the corporate and personal
levels. Companies that have been scaling back how much
they spend, such as Mr. Campanaros Total Gym, will not
have enough income to spend more on health care.
46
Other businesses are also considering halting expan-
sion until they can fgure out their next move. Franchises,
such as Visiting Angels, have held of expansion on any
new deal that is near the 50-employee mark in order to
avoid paying the hefty penalty.
47
The restaurant franchise
Bennigans has also slowed down expansion.
48
With so
many companies scared to expand, the number of un-
employed workers in the United States will not decrease.
Unemployment may even increase if these companies de-
cide to restructure their workforce toward more part-time
workers instead of full time workers, another undesired
and unintended consequence of the PPACA.
Unions are also worried that the new law require-
ARTICLE
ments will drive up costs for their health-care plans and
make unionized workers less competitive.
49
Some unions
are considering shifting workers from their current plans
to private coverage that will be subsidized by the govern-
ment or dropping insurance altogether, but this would un-
dermine a primary reason for having a union.
50
If unions
dont receive the subsidies for their lower-paid members,
companies with unionized workers can become less com-
petitive. College professors are also being afected. Many
colleges, such as Community College of Allegheny Coun-
ty in Pennsylvania, have decreased the number of classes
that adjunct professors teach to avoid having to pay their
health insurance.
51
For adjunct professors, teaching one or
two less classes can make a signifcant diference in their
salary and also the type of health insurance they will be
able to aford.
The PPACA unintentionally incentivizes companies to
restructure their workforce to keep the subsidy or avoid
the penalty. Many are considering shifting from full-time
to part-time workers and hiring more independent con-
tractors instead of employees. Companies like Elizabeth
Turleys Meesh & Mia Corp. have considered hiring in-
dependent contractors instead of increasing her staf to
keep pace with her companys rapid growth.
52
Companies
facing the PPACA are now considering hiring only part-
time employees (which companies are not required to pay
insurance for) or curbing their growth to avoid any pen-
alties. Hiring independent contractors seems less expen-
sive because companies do not pay employment taxes on
wages or health insurance premiums. However, indepen-
dent contractors come with other problems such as less
control over the hours they work and the quality of work
they produce, and also how much involvement they are
allowed to have within the business.
53
Having indepen-
dent contractors can be very complicated because tax laws
that label workers as independent contractors are subject
to interpretation, and improper classifcation may lead
to large penalties.
54
In the end, hiring independent con-
tractors to avoid the penalties will result in more unin-
sured Americans.
Some companies may also consider paying penal-
ties instead of ofering health insurance. On closer
examination, however, they may realize even if they do
take the penalty, it may still mean a large expense increase.
Business owner Rick Levi currently ofers health insur-
ance to just 25 of his 102 full time employees.
55
If he were
to ofer health insurance to all of his employees the cost
of his premiums would increase from $140,000 a year to
$500,000 a year.
56
Because he has never made a proft that
is greater than $500,000 a year, it makes sense for him to
pay the penalty of $144,000 and drop insurance entirely.
57
And last, since the PPACA is administered through the
tax code, there is an incentive for tax evasion tactics in or-
der to avoid having to pay penalties on health insurance,
using artifcial structures and legal loopholes to reduce tax
implications. These maneuvers to avoid the penalties may
result in an increase of tax planning and tax minimization.
Increased tax evasion was certainly not an intended conse-
quence of the PPACA.
Limited cost control regulations
All the problems mentioned above are signifcant for
small and medium-sized business; however, the greatest
and most unaddressed problem of the law is the lack of
cost control regulations. Not only is health insurance very
expensive for employers, but each year health insurance
will most likely become more expensive due to increasing
health care costs. Companies who ofer health insurance
now may not be able to aford higher premiums in the fu-
ture. The law ofers no way to control these rising costs. If
the cost could be controlled, then many companies would
more willing to provide health insurance for their employ-
ees, because they would know what to expect. Because
this law is so extensive, rulemaking will take another 7-10
years to complete, making it even harder for companies to
understand the impact of PPACA.
58
Potential solutions
The problems of education, perverse growth incentives,
and a lack of cost controls are signifcant issues for small
and medium-sized business. However, they are not in-
surmountable. Additional government action and private
sector solutions could limit the efects of the problems dis-
cussed above.
ARTICLE
GTTOWER.ORG | 51
Solutions for education problems
A large part of the American public is unaware of the
PPACAs implications for their lives. The publics lack of
awareness is due to the laws complexity and the govern-
ments failure to educate the public on the PPACA. The
governments education failure could be due to a lack of
desire or incentive to educate the public, lack of resourc-
es for efective education, or unawareness of how best to
educate the public. Regardless of the reasons for the lack
of government-provided education, this education failure
should be remedied. The government should have a multi-
faceted approach to educating the community on the PPA-
CA and will need assistance from a variety of sources to
reach as many people as possible. A federal agency ofce
should be specifcally tasked with coordinating all PPACA
education eforts for the public. The PPACA is adminis-
tered by at least three federal agencies: the Treasury, La-
bor, and Health and Human Services, which without a
coordinated efort, will not be able to ensure that every
aspect is covered or that the eforts are not duplicated.
This ofce could coordinate talks for parents at schools,
universities, and town hall meetings to reach large por-
tions of the public at once. Manuals and brochures should
be created to explain in simple language about the law.
There should be diferent versions for companies and for
individuals, because diferent rules apply. Online and TV
ads could also be used to inform people of the resources
available to the public. All of these educational eforts,
however, are unlikely to work efectively if opposing state
governments do not support the federal governments
work in their respective states. Other than the federal
agency ofce, public interest groups can also be used to
reach part of the community, which may not have access
to aforementioned educational outlets. The ofce should
also work with the private sector and non-governmental
organizations to help accomplish this task.
Solutions for growth limitations
Under the PPACA, a full-time employee is defned as
someone who is employed an average of 30 hours a week
or 130 hours in a month, including seasonal workers.
59

The law uses the term full-time equivalent, which refers
to employees who are not full-time employees.
60
This
means that part-time or part-time seasonal workers can be
lumped together to count as full-time employee. This def-
nition makes it even harder for companies to escape the
penalty. It also re-characterizes employees who may have
previously been considered to be part-time.
For the PPACA to avoid limiting the growth of small
and medium-sized companies as much, the law should re-
defne full time equivalent to be employees who work 40
hours per week, the more typically understood defnition,
reducing confusion for business and employees. The law
should also eliminate the full-time equivalent employee
defnition. Because part-time employees are lumped to-
gether into a single full-time equivalent employee, com-
panies may struggle to determine which employees are
covered by the law. By clearly distinguishing between
part-time and full-time employees, it will be easier to mon-
itor compliance with the PPACA.
In addition, to help minimize growth limitations, it
should be possible for small companies to add employees
without the harsh efects of losing subsidies and gaining
penalties. A transition could be introduced to ease the bur-
den of having to provide insurance immediately. Compa-
nies that have between 26-49 employees are unsure of what
to do. They have no subsidy to help pay for their employ-
ees health insurance, but they also have no penalty if they
dont provide health insurance. These companies should
be ofered a smaller subsidy to help incentivize them to
ofer health insurance. Having this smaller subsidy
61
will
also ease the growing pains that companies with 25 or less
employees would otherwise feel by suddenly losing the
entire subsidies by adding a single full-time equivalent
employee. Small companies could lose 1.4% of the sub-
sidy for every employee over 25, so that by the time the
company reaches 50 employees the subsidy will have been
eliminated gradually.
This, however, is not a perfect solution. Ofering more
subsidies will radically increase the cost of the PPACA for
the government. The government would have to provide
money for the program that it currently does not have. Its
possible that the greater funding could be ofset by the
fact that broader coverage will get more people involved
ARTICLE
in the program and health care costs could be spread over
more people. Of course, some people or political parties
would oppose the fact that now the law would cover even
more people, creating further challenges to implementing
and regulating the law. The PPACA, however, will still
take many years to be fnalized and implemented so this
change could occur later. It could come into efect in 2020,
which would give the government time to decrease the
current defcit and acquire the funds needed to implement
it.
Companies may have to choose between the PPA-
CAs incentives to constrain growth or ofering lower cost
health insurance. To surmount the growth constraints by
lowering the cost of health insurance, some companies
may choose to redesign their health insurance plans, al-
lowing for diferent ways to distribute or absorb costs,
which could lessen the growth efects. Companies may
choose to ofer Consumer Driven Health Plans (CDHP),
self-funded plans, or use cost-shifting. CDHPs are ap-
pealing because they cost nearly 25% less than Preferred
Provider Organization (PPO) plans.
62
Having self-funded
plans can ofer employers more fexibility when it comes
to designing their insurance plans. Self-funded plans also
ofer more control over beneft design by beter analysis to
loss and trend data.
63
Reserves are set aside to pay claims
out of current cash fows as they arise.
64
The last way that
a company can redesign its plan is by shifting more costs
onto employees. Cost-shifting can mean increasing co-
pays, out-of-pocket maximums and deductibles. Using
cost-shifting tactics may make companies less competitive
because they will be less atractive to employees compared
to other companies who ofer more health coverage. Shift-
ing costs to employees can also be tricky because if too
much cost is placed on the employee, companies can be-
come subject to insufcient coverage penalties, which are
$2,000 per employee.
Small businesses can also choose to enter into a SHOP
(Small Business Health Options) program.
66
Many
small businesses pay up to 18% more for health insur-
ance than larger businesses because of administrative
costs.
67
By joining a SHOP program, a small com-
pany can increase its purchasing power by uniting
with other small companies, ofering beter quality health
insurance choices at lower costs and also pool their risk to
decrease their costs.
68
Solutions for limited cost control regulations
Ironically, the rising costs of healthcare helped create the
PPACA, but the PPACAs failure to use genuine cost con-
trols is also its greatest weakness. The fact that the PPA-
CA has no way to control future healthcare costs makes it
more challenging to accept. National health spending is
projected to continue to grow faster than the economy, in-
creasing from 18% ($2.8 trillion) to about 25% of the GDP
by 2037. Federal health spending is projected to increase
from 25% to approximately 40% of total federal spend-
ing by 2037.
69
This high level of spending will afect how
people deal with the PPACA but also how the government
deals with all other government expenditures. Because
of the rapidly increasing expenditures on healthcare, the
governments resources available for other projects, such
as education and infrastructure investments, will be de-
creased signifcantly. One way to prevent healthcare costs
from crowding out other spending is to control growth in
healthcare costs, for both public and private payers.
70
Competitive bidding should be expanded to include
more aspects of health care to drive down costs. Competi-
tive bidding is a way to acquire bids by openly advertis-
ing the scope, specifcations and terms and conditions of
the proposed contract as well as the criteria by which the
bids will be evaluated.
71
The purpose is to obtain goods
and services at the lowest price by stimulating competi-
tion, and by preventing favoritism.
72
Competitive bidding
has already been successful: Medicare was able to reduce
its spending on wheelchairs by 42% using this technique.
73

The PPACA requires that Medicare expand competitive
bidding for equipment, prosthetics, orthotics, and sup-
plies to all regions by 2016.
74
Medicare should also extend
competitive bidding to medical devices, laboratory tests,
radiologic diagnostic services and all other commodities.
75

The competitive bidding process should be monitored by
a panel of business and academic experts to ensure that
its used in a productive manner. The process should also
require that insurance exchanges conduct competitive bid-
ARTICLE
GTTOWER.ORG | 53
ding on behalf of private payers and state employee plans.
76

When creating a competitive bidding plan, the quality of
the services should be closely monitored to ensure the pro-
cess is done correctly because companies may drive down
quality in order to ofer cheaper services. Lower quality
could cause people with more means to look elsewhere for
their healthcare services, which could result in the system
falling apart by having less people involved and resulting
in high premiums.
More than 75% of physicians face a malpractice claim
over the course of their career.
77
The large number of mal-
practice claims results in the practice of defensive medi-
cine, which increases the costs of healthcare but not neces-
sarily the quality of care. In defensive medicine, doctors
may be more worried about saving their careers than their
patients. Defensive medicine is the practice of diagnostic
or therapeutic measures conducted primarily not to en-
sure the health of the patient, but as a safeguard against
possible malpractice liability.
78
To decrease defensive
medicine, a safe harbor could be created in which physi-
cians would be presumed to have no liability if they used
qualifed health-information-technology systems and ad-
hered to evidence-based clinical practice guidelines.
79
A
safe harbor system could be used to present evidence in
the early stages of litigation and have a judge rule on mal-
practice cases instead of engaging in a courtroom batle.
80

A safe harbor could signifcantly lower doctors malprac-
tice insurance costs because malpractice cases would be
resolved much faster and in a more efcient way. This
would also imply that doctors wouldnt be as afraid of
giving a wrong diagnosis (given it isnt life threatening)
and may also reduce the number of unnecessary tests con-
ducted on patients. An initiative called Choosing Wisely is
developing these guidelines.
81
Choosing Wisely is a group
of leading physician groups that have already released
guidelines on 45 common tests that are overused or un-
necessary.
Another way to limit healthcare costs is to have
states, with the encouragement of federal grants, set an
overall health-cost cap covering both public and private
spending.
82
Massachusets, the state plan on which the
PPACA is modeled, has recently adopted such limits, and
Maryland has capped hospital spending.
83
Health cost
caps are essential because healthcare costs will not be de-
creased by simply shifting the cost from government onto
health insurance companies, then onto business, and ulti-
mately onto individuals. Panels of independent counsels
composed of providers, payers, businesses, consumer and
economists should be created to set the spending target.
84

An independent panel could minimize political agendas
from inhibiting the creating of this cost controlling mecha-
nism.
If health care costs arent controlled and payers contin-
ue to shift costs onto individuals, healthcare will become
even more costly. Extremely high healthcare costs will
likely lead to people severely restricting their consump-
tion of healthcare and they might forego necessary care.
Failing to control healthcare costs can lead to bad out-
comes for business, the government, and the public.
Conclusions
After analyzing many parts of the PPACA, its evident that
the creation of this law was a positive step for 50 million
uninsured Americans; the PPACA is not, however, a per-
fect solution. The PPACA still has a long journey ahead to
become a beter solution. The PPACA has many problems
regarding the lack of public education and awareness,
perverse growth incentives for small and medium-sized
companies, but most importantly its lack of cost control
mechanisms. The most dangerous consequences could be
avoided if the PPACA provided more efective controls for
rising health care costs.
An unfortunate consequence of the PPACA is that com-
panies are afraid to invest more in the healthcare of their
employees. Companies fear that health insurance costs
will keep rising each year with no way to slow them down
or control them. Companies perceive that investments in
health insurance would not just be for one year, but would
increase each year. If companies could predict how much
they would have to pay by controlling the cost of health-
care, it would be easier to predict the best approach to the
PPACA.
As the PPACA shifts health insurance from a market-
based system to a solidarity-based system, everyone will
ARTICLE
pay for the small number of people who are consuming
most of the healthcare in the country. Because there is no
annual limit on the amount of annual healthcare cover-
age given to a person anymore, the only way to control
the amount people will pay is by controlling the costs of
healthcare. In the end, the PPACA has the potential to be
a great solution for the United States. However, there are
many aspects that remain to be addressed and many years
of implementation to observe its actual efects on all busi-
nesses and on the public.
Acknowledgements
This paper was prepared during an independent research course under
the direction of Professor Karie Davis-Nozemack.
Footnotes
1. Lea Winerman, President Obama Signs Health Reform Into Law,
PBS NEWSHOUR (March 23, 2010, 12:19 PM), htp://www.pbs.
org/newshour/rundown/2010/03/president-obama-signs-health-
reform-into-law.html.
2. Ken Shots & Alexander Hirsch, STAN. GRADUATE SCH. OF
BUS., CASE NO. P74, HEALTH CARE REFORM: 2009-2010 (2011).
3. Id.
4. Id.
5. Michael Lee, Jr., Trends in the Law: The Patient Protection and
Afordable Care Act, 11 YALE J. HEALTH POLY L. & ETHICS 1
(2011).
6. Id. at 2-3.
7. Id. at 2.
8. Id. at 2.
9. Id.
10. James P. Pffner, President Clintons Health Care Reform Propos-
als of 1994, in TRIUMPHS AND TRAGEDIES OF THE MODERN
PRESIDENCY 69 (David Abshire, ed., 2001).
11. Shots & Hirsch, supra note 2.
12. Patient Protection and Afordable Care Act, Pub. L. No. 111-148,
124 Stat. 119 (2010).
13. Id.
14. Id.
15. Id.
16. Will Dunham, Timeline: Milestones in Obamas Quest for
Healthcare Reform, REUTERS (Mar. 22, 2010, 1:50 AM), htp://
www.reuters.com/article/2010/03/22/us-usa-healthcare-timeline-
idUSTRE62L0JA20100322.
17. Patient Protection and Afordable Care Act.
18. Phil Galewit, Consumers Guide to Health Reform,
KAISER HEALTH NEWS (Apr. 13, 2010), htp://www.kaiser-
healthnews.org/Stories/2010/March/22/consumers-guide-health-
reform.aspx.
19. Lee, supra note 5.
20. Id.
21. Robert Pear, Rules Let Youth Stay on Parents Insurance, N.Y.
TIMES, May 11, 2010, at A11. See also Young Adults and the Af-
fordable Care Act: Protecting Young Adults and Eliminating Bur-
dens on Families and Businesses, THE WHITE HOUSE, htp://
www.whitehouse.gov/sites/default/files/rss_viewer/fact_sheet_
young_adults_may10.pdf (last visited May 30, 2013).
22. For the purpose of this paper, small companies will be defned
as those with 25 or less employees. Medium-sized companies are
those with 26-49 employees and large companies are those with 50
or more employees.
23. Lee, supra note 5.
24. Id.
25. Patient Protection and Afordable Care Act (PPACA), PA. SMALL
BUS. DEV. CTR., htp://pasbdc.org/ppaca (last visited May 30,
2013).
26. Id.
27. Id.
28. Id. See also Galewit, supra note 18.
29. PA. SMALL BUS. DEV. CTR., supra note 25.
30. Fair Labor Standards Act Advisor, U.S DEPT. OF LABOR, htp://
www.dol.gov/elaws/faq/esa/fsa/014.htm (last visited May 30,
2013).
31. Sarah Klif, Millions Will Qualify For New Options Under The
Health Care Law. Most Have No Idea, WASH. POST (Nov. 21,
2012, 8:30 AM), htp://www.washingtonpost.com/blogs/wonk-
blog/wp/2012/11/21/millions-will-qualify-for-new-options-under-
the-health-care-law-the-vast-majority-have-no-idea/>.
32. Id.
33. Bill Barrow, Obamacare Faces Near-Solid Block In The South,
HUFFINGTON POST (Mar. 30, 2013, 4:03 PM), htp://www.huf-
ingtonpost.com/2013/03/30/obamacare-block_n_2985587.html.
34. Id.
35. Id.
36. Focus on Health Reform: Summary of New Health Reform Law,
KAISER FAMILY FOUND., (April 23, 2013), htp://kaiserfamily-
foundation.fles.wordpress.com/2011/04/8061-021.pdf.
37. Emily Maltby, New Insurance Regulation Will Go By Size of Com-
panies Staf in 2013, WALL ST. J., Jan. 16, 2013, at B4.
38. Id.
39. Id.
40. Id.
41. PA. SMALL BUS. DEV. CTR,, supra note 25.
42. Id.
43. Id.
44. Id.
45. Emily Maltby & Angus Loten, Small Firms Scramble To Redraw
ARTICLE
GTTOWER.ORG | 55
ARTICLE
Plans, WALL ST. J. (Jan. 2, 2013, 9:08 PM), at htp://online.wsj.
com/article/SB10001424127887323374504578218283972873250.
html?mod=WSJ_SmallBusiness_LEFTTopStories.
46. Id.
47. Id.
48. Id.
49. Kate Rogers, Franchises Squeezed Tightly by Health-Care Law,
FOX SMALL BUS. CTR., (January 10, 2013), htp://smallbusiness.
foxbusiness.com/legal-hr/2013/01/10/franchises-squeezed-tightly-
by-health-care-law/.
50. Id.
51. Janet Adamy & Melanie Trotman, Some Unions Grow Wary of
Health Law They Backed, WALL ST. J., Jan. 30, 2013, at A1.
52. Id.
53. Id.
54. Mark Peters & Douglass Belkin, Health Law Pinches Colleges,
WALL ST. J., Jan. 18, 2013, at A3.
55. Emily Maltby, A Health Scare for Small Businesses, WALL ST. J.,
Jan. 16, 2013, at B1.
56. Id.
57. Id.
58. Emily Maltby & Sarah E. Needleman, Some Small Businesses Opt
for the Health-Care Penalty, WALL ST. J., Apr. 8, 2013, at B1.
59. Id.
60. Id.
61. Lisa R. Nelson, Managing Employer Costs in the Post-PPACA
World, ABA HEALTH ESOURCE (July 2011), htp://www.ameri-
canbar.org/content/newsleter/publications/aba_health_esource_
home/aba_health_law_esource_1107_nelson.html).
62. Maltby, supra note 37.
63. Id.
64. The subsidy of 35% will reduce by 1.4% to gradually reach 0% by
50 employees. This number will change depending the amount of
subsidy each company is receiving and can be found by dividing
the percent of subsidy by 25 (35/25=1.4).
65. Nelson, supra note 61.
66. Id.
67. Id.
68. Id.
69. Employers with Fewer than 25 Employees, U.S. SMALL BUS. AD-
MIN., htp://www.sba.gov/content/employers-with-fewer-25-em-
ployees (last visited May 30, 2013).
70. Id.
71. Id.
72. Ezekiel Emanuel, et al., A Systematic Approach to Containing
Health Care Spending, 367 NEW ENG. J. MED. 949 (2012).
73. Id.
74. What is competitive bidding?, BUSINESSDICTIONARY.COM,
htp://www.businessdictionary.com/defnition/competitive-bid-
ding.html (last visited May 30, 2013).
75. Id.
76. Emanuel, supra note 72.
77. Id.
78. Id.
79. Id.
80. Id.
81. What is Defensive Medicine?, DEFENSIVEMEDICINE.ORG,
htp://defensivemedicine.org/what-is-defensive-medicine/ (last
visited May 20, 2013).
82. Emanuel, supra note 72.
83. Id.
84. Id.
85. Ruth Marcus, Taking Health-Care Reform A Step Further,
WASH. POST (August 16, 2012), htp://www.washingtonpost.
com/opinions/ruth-marcus-taking-health-care-reform-a-step-
further/2012/08/16/1c76542e-e7d4-11e1-936a-b801f1abab19_story.
html.
86. Id.
87. Id.
Shannon Kehoe
1
& Vicki Birchfeld, PhD
1
I mmi gr at i on t r ends and at t i t udes : I s t he
Uni t ed Ki ngdom an anomal y?
In recent years, Europe as a whole has undergone a shift in
immigration. However, some countries have born a greater
share of this infux than others. Germany and France, for
example, have received more immigrants than average,
but have not experienced the same invasion of immi-
grants as has Italy (Transatlantic Trends, 2011). Mean-
while, though the United Kingdom has experienced
an increase in immigrants, it has not received nearly the
total number of immigrants seen in Germany or France,
nor experienced the dramatic increase in numbers as has
Italy (Transatlantic Trends, 2011). Similarly, the percent-
age of immigrants in the population failed to ofer much
explanation. Despite this, in the 2011 Transatlantic Trends
Survey the United Kingdom showed a much more nega-
tive opinion towards immigration than did Italy, France,
or Germany.
Two potential explanations of the diference in ati-
tudes between the United Kingdom in contrast to those of
France, Germany, and Italy include unemployment rates
and the type of immigration policy in the country. High
domestic unemployment is often cited by politicians as
a reason to restrict immigration. This political discourse
may infuence public opinion. Immigrants are also com-
petitors in the job market, and may or may not have a job
upon arriving in their destination country. Immigration
policy is the way in which governments manage or mis-
manage immigrants (Tejera, 2011). The manner by which
immigrants are treated by the government has the poten-
tial to signifcantly impact how society accepts, or rejects,
immigrants. Therefore, it is hypothesized that:
1. Countries with high unemployment will have a more
negative atitude toward immigrants than will coun-
1
Sam Nunn School of International Afairs, Ivan Allen College of Liberal Arts, Georgia Institute of Technology. Correspondence
should be addressed to TL (skehoe3@gatech.edu).
In recent years Europe as a whole has undergone a shift
in immigration. Germany, France, and Italy have all ex-
perienced signifcant increases in the number of immi-
grants they receive each year, but their atitudes towards
immigrants have remained rather stable. The United
Kingdom, on the other hand, has not experienced a sig-
nifcant change in the number of immigrants, but has
drastically altered its atitude towards them. This study
examines unemployment levels and immigration policy
as potential causes for the diferent atitudes, but fnds
that neither of these variables contribute to the varying
atitudes observed. As such, the study recommends fur-
ther analysis into whether diferences in religion and
foreign direct investment contribute to the diferent at-
titudes towards immigration, as well as a more intense
study of the use of a cap in immigration policy.
ARTICLE
GTTOWER.ORG | 57
ARTICLE
tries with a low level of unemployment.
2. Countries with an integration program will have more
positive atitudes toward immigration than countries
without an integration program.
3. Countries with an immigration cap will have a more
negative atitude towards immigration than will coun-
tries without an immigration cap.
Immigration atitudes
Past research has connected anti-immigration atitudes
to the perception that immigration leads to higher levels
of unemployment, even though this perception may not
have any factual basis to support it. A 2002 study on at-
titudes towards foreigners in the European Union found
empirical evidence that, at best, the impact of immigrants
on European labor markets is inconclusive, often fnding
small efects of immigration on unemployment, where-
as atitudes towards immigration may be infuenced by
rumors and stories reported in the media(Gang, Rivera-
Batiz, & Yun, 2002). Indeed, a 2000 study based on the
British Social Atitude Survey found that racial atitudes
are strongly associated with hostility to immigration from
ethnically distinct populations (Dustmann & Preston,
2000). In a 1998 study on Canada and the United States, it
was found that 49% of Canadians believed that immigra-
tion increased unemployment among people already liv-
ing in the area (Esses, Jackson, & Armstrong, 1998).
On the other hand, there is also research to support
that economic strains do not necessarily lead to higher lev-
els of xenophobia. Krueger and Pischkes study on crime
against foreigners in (unifed) Germany found no relation-
ship between the amount of crime against immigrants and
the rate of unemployment in an area (Pischke & Krueger,
1997). This observation must, however, be qualifed by the
fact that physical violence is a much stronger expression
of discontent than merely marking down an answer for a
survey, and thus there is likely to be a smaller expression
of discontent through physical violence, and a larger ex-
pression of discontent through statistical survey data.
German immigration policy
Immigration policy is a logical, potential explanation for
the negative perception of immigration in the United
Kingdom as immigration policy is a determining factor
not only in how many immigrants a country accepts, but
also in how accepted these immigrants are by their native-
born neighbors. Two decades ago, Germany shared the
United Kingdoms negative perception of immigration
(Suessmuth, 2009). Indeed, only since the policy shift
that began in 2000 has the perception that Germany is
not a country of immigration changed. This change was
achieved via the implementation of legislation aimed at
integrating immigrants, and specifcally recruiting immi-
grants with the types of skills needed to decrease struc-
tural unemployment. Structural unemployment is a situ-
ation where workers lack jobs because the skills possessed
do not ft the jobs available in their environment (Cam-
bridge University Press, 2013). It was not achieved by an
immigration cap; such a cap was not the focus of the legis-
lation (Mnz, 2004). The legislation used in Germany still
permited immigration, but streamlined the immigration
process to fll positions that the German work force could
not.
French immigration policy
France has revised its immigration policy in the past de-
cade. In 2003 France began requiring all immigrants to
sign an integration contract in return for permission
to remain in the country (Zappi, 2003 ). This contract re-
quires immigrants to undergo language training and in-
struction on the values of French society. Those who
successfully complete the program are awarded a 10 year
residence permit, while those who do not receive a permit
for 1 year only. While this law focuses on the integration
of immigrants, according to Zappi, its primary objective
is to cap, or at least limit, the number of foreigners with
the ability to enter France; however, there is no ofcial im-
migration cap in France. In addition, unlike in Germany,
optimizing the type of immigrants permited entrythe
types of skills they bring to the work force-- is not a fac-
tor in French immigration law. While French immigration
law is concerned primarily with integrating immigrants, it
also contains signifcant provisions for limiting their num-
ber without specifcally utilizing an immigration cap.
ARTICLE
Italian immigration policy
Italian laws to regulate immigration difer from those of
both France and Germany, most notably in the fact that it
was only in 1990 that Italy acquired norms with which to
regulate immigration at all (Aquila, 2012). That is, limiting
immigration in Italy is a relatively new phenomenon, with
the Martelli Law-- the basis of modern Italian immigration
law having been passed in 1998. These reforms in Italy
implemented measures for establishing immigrant quotas
(also known as caps), beter integrating Italian migrants,
and the establishment of detention periods for the expul-
sion of illegal immigrants and immigrants who overstay
their visas (Paparella & Rinolf, 2002).
More recent reforms to the initial laws include extend-
ing the detention period for immigrants applying for visas
in Italy. In 2002, the maximum detention period for an
immigrant waiting to enter Italy was raised to 60 days; in
2008 it was raised to 180 days; in 2011, the detention peri-
od was extended to 18 months (Paparella & Rinolf, 2002).
Due to the long waiting period for acquiring residency or
work permits in Italy, combined with the long period of
permited stay without such permits, Italian immigrant
communities have managed to mobilize, and have begun
demanding amnesties that would permit the regulari-
sation of the situation of immigrants already present for
years on Italian territory, but who had overstayed their
alloted period of stay without a residence permit.
English immigration policy
The United Kingdom uses an immigration cap. However,
the United Kingdom does not have any kind of policy for
the integration of immigrants in place. In November of
2010 the government of the United Kingdom implement-
ed new immigration policy, which included a permanent
cap of 21,700 on skilled immigrationless than half the
number recommended by the governments own Migra-
tion Advisory Commitee (Workpermit.com, 2012). In
addition, this policy prioritises workers earning
40,000 or more (Anonymous, 2010). According to a
2010 article from the Economist, in 2009 less than
of non-EU migrants came because of work; the ef-
ciency of these new immigration laws is currently
quite hotly debated (The Economist, 2010). According to
the Migrant Integration Policy Index, the recent immigra-
tion reforms have decreased the ability of immigrants to
integrate themselves in the United Kingdom (The Migrant
Integration Policy Index, 2013).
Methods
The dependent variable Atitude towards Immigration
was measured by whether immigration was perceived as
a problem, or as an opportunity, and the perception of
how well immigrants are able to integrate with the native
population. The independent variable of Number of Im-
migrants was measured via World Bank data on the Total
International Migrant Stock, as well as by International
Migrant Stock, Percent of Population. The dependent
variable Immigration Policy was measured by whether
or not a capmaximum number of immigrantswas in
place, and by the existence of a policy for the integration
of immigrants with the native born population, which was
measured by examining the countries score on the Mi-
grant Integration Policy Index (also called the MIPI index).
The level of unemployment, another dependent variable,
was measured via data from the World Bank on unem-
ployment as a percent of the total labor force. Due to the
amount of data made available by both the World Bank,
and the study examined only the period from 2005 to 2011.
Defning immigration
First, it is important to note that immigration refers
specifcally to people arriving for permanent residence
in a country other than the one in which they were born
(Merriam-Webster, 2013). International Migrant Stock, as
defned by the World Bank, is the number of people born
in a country other than that in which they live, including
refuges (The World Bank, 2013). Though the data source
in this study difered from those used in the 2011 Transat-
lantic Trends Survey, the source used the same defnition
of immigrant and thus measured the same thing.
The World Bank data set contains two diferent mea-
sures of immigration. The frst measure, International
Migrant Stock, Total measured the raw, total count of mi-
grant stock in a country, whereas International Migrant
GTTOWER.ORG | 59
ARTICLE
Stock, Percent of Population measured that same count,
but as a percent of the native born population (The World
Bank, 2013). In order to improve the accuracy and preci-
sion of this study, both of these measures were used (Fig.
1).
Atitudes towards, and integration of, immigrants
Atitude towards immigration was operationalized via 2
individual surveys conducted by the 2011 Transatlantic
Trends Survey: whether immigration is perceived as more
of a problem than an opportunity, and the perception of
how well immigrants are able to integrate with the coun-
trys native population. Each of these individual measures
does measure atitude of the population towards immi-
grants, but each measures this atitude slightly diferently.
The former measures purely the populations atitude to-
wards immigration, and whether this atitude is positive
or negative. The later measures how well the population
perceives the integration of immigrants; how connected
the native population feels to the immigrant population.
This was an important statistic to compare to the MIPI in-
dex, which was used to measure Immigration Policy.
The Migrant Integration Policy Index (MIPI or MI-
PEX) was one of two methods used to evaluate Immigra-
tion Policy. The MIPI uses 148 diferent policy indicators
on migrant integration divided among 7 policy areas in
order to measure how accepted immigrants are in a coun-
try (Migrant Integration Policy Index, 2013). Each indica-
tor is then given a score between 1 and 3 points, 3 being
the highest. The scores are then averaged to calculate an
average policy score for each policy area. These individu-
al policy area averages are then added together and aver-
aged again to give a fnal integration score for the country.
MIPI data is available for the years 2007, and 2010, thus
these are the two years used for comparison in this study.
In addition to the MIPI index, countries were also ex-
amined based on the type of immigration policies they
used. Specifcally, countries were examined to see wheth-
er or not an immigration cap was used. An immigration
cap is a limit on the number of immigrants allowed to en-
ter a county, and is set by a countrys government. The
immigration cap is an important policy tool to examine as,
if a government lowers the immigration cap, but the num-
ber of immigrants arriving to a country remains constant,
it may seem as though more immigrants are arriving than
in previous years and cause greater concern among the
population. However, it may simply be the case that the
same number of immigrants are arriving, but less of them
are deemed legal. In addition, a cap on immigration is
one of the most recent, and largest, changes to British im-
migration policy, and may be factor in how immigration is
perceived in this region.
Measuring unemployment
Finally, as mentioned in the introduction, unemployment
was another independent variable examined in this study.
In order to measure the level of unemployment in a coun-
try, data from the World Bank Indicator Unemployment,
total (% of total Labor Force) was used. As defned by the
World Bank, this measure refers to the share of the labor
force that is without work but available for and seeking
Figure 1 French, German, Italian, and English international
migrant stock. (A) Total number of immigrants and (B) immigrant
stock as a proportion of the population. Black bars = 2005 data;
White bars = 2010 data. Data was provided by the World Bank Data-
bank (The World Bank, 2013).
ARTICLE
employment (The World Bank Group, 2013). Data was
collected on an annual basis. However, the World Bank
notes that defnitions of Labor Force and unemploy-
ment vary by country; the data are all measures of un-
employment, but a diferent method of measurement may
have been used in some cases. For the purposes of this
study, however, this method of measurement is sufcient.
Data Analysis
Having decided upon the methods of measurement for
each variable, available data were collected and compared
across the years 2005 to 2011. The dependent variable
of Atitude towards Immigration was broken into two
measurements: perception of immigration as a prob-
lem, or an opportunity, and the perceived ability of
immigrants to integrate. These two measures were
then compared to the percent unemployment, the
total number of international migrant stock, the
percent international migrant stock, the MIPI score, and
the presence of a cap on immigration in order to exam-
ine why the United Kingdom recorded a more negative
atitude towards immigration in the 2011 Transatlantic
Trends Survey than did France, Germany, or Italy.
Results
Unemployment
While France, Germany, and the United Kingdom all con-
tained similar numbers of immigrants in 2005 and 2010
international migrant stock as a total count, as well as a
percent of population, proved insignifcant they dif-
fered signifcantly in regards to Unemployment, and MIPI
score. France and Germany tracked similarly regard-
ing their view of Immigration as more of an opportunity
than a problem, but difered regarding unemployment.
Between 2008 and 2009, France experienced nearly a 2%
increase in unemployment, compared to Germanys .2%
increase (Fig. 2). The United Kingdoms experience was
similar to that of France, experiencing nearly a 3% increase
in unemployment between 2008 and 2009. In 2010 how-
ever, unemployment in Germany and the United King-
dom continued to increase; yet, the increase amounted to
merely .1% and .2%, respectively. In 2010, unemployment
decreased by .2% in Germany. Italy experienced a signif-
cant increase in unemployment in all three years.
Immigration policy
The fact that France and the United Kingdom both expe-
rienced a signifcant increase in unemployment between
2008 and 2009 is important as each also experienced a 4%
increase in the number of citizens who perceived immi-
gration as a problem. However, Germany, which did not
experience unemployment on the same scale as France of
the United Kingdom, also experienced a similar increase
in the number of people who perceived immigration as
a problem (5%), and in Italy 4% fewer people saw immi-
gration as more of a problem than an opportunity, even
though unemployment has increased in Italy since 2008.
Though France and the United Kingdom had similar
experiences regarding immigrant numbers and unem-
Figure 2 Unemployment in France, Germany, Italy, and UK.
While all countries depicted here experienced an increase in unem-
ployment between 2008 and 2009, Germany was the only country
in which unemployment decreased between 2009 and 2010. Data
was provided by the World Bank Databank (The World Bank Group,
2013).
GTTOWER.ORG | 61
ARTICLE
ployment, they utilized very diferent policies, and scored
very diferently in the Migrant Integration Policy Index.
France received the same MIPI score in 2010 as in 2007.
The United Kingdom received ten points less. In addi-
tion, while the United Kingdom makes use of an immigra-
tion cap (implemented in 2010), France does not. Despite
these diferences, France and the United Kingdom both
experienced a 4% increase in respondents who viewed im-
migration as a as more of a problem than an opportunity
between 2008 and 2009. The United Kingdom still polled
far more negatively than did France, but the two countries
experienced similar shifts in responses despite their difer-
ences in immigration policies.
Italys view of immigration as a problem decreased
between 2008 and 2009, even though the number of im-
migrants received and the percentage of the population
without work increased far more than in any other coun-
try. Despite this, Italys MIPI score decreased by only a
single point. This contradicts the original hypothesis that
increased unemployment causes increased negative ati-
tudes towards immigration.
Societys perception of immigrant integration
Of particular interest, however, is the picture given when
the perceived ability of immigrants to integrate in a coun-
try is compared to that countrys MIPI score. While Ger-
many ranks as the 2nd highest of the four countries in
terms of overall MIPI score, it ranks 4th of 4 countries with
regard to the perceived ability of immigrants to integrate
well with the native population (Fig. 3). This is despite the
fact that Germany had the lowest unemployment levels,
and 66% of the population saw immigration as more of an
opportunity than a problem (of the four countries exam-
ined in this study, only France had a higher percentage)
(Transatlantic Trends, 2011). The MIPI policy scores do
not align with the public perceptions of policy efects.
Finally, the presence of an immigration cap, formal
or implied, was not found to be signifcant with regard to
public opinion towards immigration. The United King-
dom and Italy, for example, both had ofcial immigration
caps, but Italy recorded a positive view of immigration
in 2011, while the United Kingdom recorded a negative
view. France, while it did not have a formal immigration
cap, but did have legislation that essentially informally es-
tablished one, scored a negative view of immigration as
well. Despite both having utilized an immigration cap,
the United Kingdom and Italy recorded very diferent at-
titudes towards immigration in 2011.
Discussion
The data in the results section do not fully support the
original hypotheses that 1) countries with high unemploy-
ment would have a more negative atitude towards im-
migration, 2) that countries with a high MIPI score would
view the ability of immigrants to integrate more positively,
and 3) that countries with an immigration cap would have
Figure 3 Country stratifcation of the 2010 MIPI score and per-
ceived ability of immigrants to integrate. Both the overall score
from the Migrant Integration Index (overall MIPI score, in black bars)
and the percentage of people who perceived immigrants as able to
integrate well or very well (in yellow line) are depicted. The MIPI
score is a raw score (left axis), whereas the perception of immigrant
ability to integrate is measured as a percent (right axis). Data was
provided by the Migrant Integration Policy Index and the 2011
Transatlantic Trends Survey (Transatlantic Trends, 2011; Migrant
Integration Policy Index, 2013).
ARTICLE
more negative atitude towards immigration than would
those without. France and the United Kingdom experi-
enced an increase in unemployment and an increase in the
number of people who viewed immigration as a problem,
as was hypothesized. Italy, however, experienced an in-
crease in unemployment, but no increase in the number of
people viewing immigration as a problem, which contra-
dicted the original hypothesis that countries with higher
unemployment would hold more negative opinions of
immigration. Indeed, the number of Italian people who
viewed immigration as more of an opportunity increased
in 2011. Meanwhile, the expectation that a country with
a high MIPI score and a high number of people with a
positive perception of immigrant ability to integrate was
not supported; at least, not in the case of Germany. Ger-
many was near the top of the four countries in terms of its
overall MIPI score, but ranked last of the four countries in
terms of societys perception of the ability of immigrants
to integrate. The presence of an immigration cap was not
found to be connected with the perception of immigrants
as, though both the United Kingdom and Italy made use
of an immigration cap, in 2011 the United Kingdom re-
corded a negative perception of immigration, and Italy a
positive one.
Further Research
As the Migrant Integration Policy Index scores did not
align as anticipated, with Germany ranked second highest
via its MIPI score, but lowest with regard to the publics
perceived ability of immigrants to integrate, this connec-
tion, or, more aptly, misconnection between the actual ef-
fects of policy and the publics perception of those efects
is an area for further research and exploration. Because
the hypotheses examined in this paper did not hold up,
further research must be done in order to explain the vari-
ation in atitudes towards immigration in Europe. Spe-
cifcally, an analysis of atitudes towards religion, the
amount of Foreign Direct Investment, and a more in-
tense analysis of immigration cap policy may prove
noteworthy.
As the immigration caps in Italy and the United
Kingdom are relatively recent developments (Italy
passed legislation for a cap in 1998, the United Kingdom in
2010), it may prove benefcial to reexamine the connection
between an immigration cap and the negative perception
of immigration as more precisely defned and descriptive
data on immigration cap policies in these countries be-
come available.
Atitudes towards religion may, as well, prove benef-
cial to examine due to the recent religious conficts, and
the decidedly intense and global increase in religious in-
tolerance. It would prove, at the least, interesting to see
whether or not higher levels of religious tolerance corre-
lated with higher levels of anti immigration atitudes (Pew
Forum on Religious and Public Life, 2012).
Finally, a study on whether or not the amount of For-
eign Direct Investment to a country may ofer something in
the way of explaining the varying atitudes to immigrants
in Italy, the United Kingdom, France, and Germany. That
is, does the amount of Foreign Direct Investment from one
country to another impact how the immigrants from the
investing country are perceived by citizens of the country
being invested in?
Neither the type of immigration policy used, nor the
level of unemployment, explained the variation in ati-
tudes to immigration in Italy, the United Kingdom, France,
or Germany. However, further research and analysis with
more precise defnitions of immigration cap policies, the
perceptions of Religion, and the amount of Foreign Direct
Investment may prove the explanations that unemploy-
ment and immigration policy, here, could not.
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ARTICLE
Emily Robey-Phillips
1
, Gillen Heisler
1,2
, & Victoria Wall
1
, Christopher Brown
1
& Peter Brecke, PhD
1
Chi l d and mar r i age cul t ur e, womens
i nf l uence out s i de t he home, s ex and STI
educat i on, and homos exual r i ght s
While homosexual rights have been a controversial top-
ic for several decades, Russias hosting of the Winter
Olympics has recently brought even more global at-
tention to the topic. The Russian law targeting homosexu-
al propaganda, however, is just one example of laws on
homosexuality worldwide. While there have been many
studies about homosexual rights within certain countries,
there have been extremely few that examine homosexual
rights at the state level. Furthermore, extremely few fac-
tors that impact a countrys level of homosexual rights
have been studied. This paper hopes to address the gap
in the literature by addressing the question: what factors
impact the level of rights aforded to homosexuals?
Childbearing, childrearing, and marriage culture
Few studies have linked homosexual rights to childbear-
ing, childrearing, and marriage culture (CCMC); however,
several show the relationship between CCMC and indi-
vidual choice in marriage. Dyson and Moore found that
kinship structure in India impacts womens standing in
marriage (1983). For example, higher infant mortality is
linked to a greater societal value on childbirth. In areas
with higher infant mortality, women are younger both
when they are frst married and at the birth of their frst
child. In these areas, women have less choice in husband
selection. In areas with a lower infant mortality rate, the
1
Sam Nunn School of International Afairs, Ivan Allen College of Liberal Arts, Georgia Institute of Technology.
2
Ernest Scheller Jr.
College of Business, Georgia Institute of Technology. Correspondence should be addressed to ERP (ea.robey@gmail.com).
Despite the modern political debate on homosexual
rights, litle research has been conducted on the interna-
tional scale on the topic. This research uses regression to
examine the factors that impact homosexual rights on a
global scale, focusing on childbearing, childrearing, and
marriage culture (CCMC), womens infuence outside
the home (WIOH), and Sex and Sexually Transmited
Illnesses (STI) Education (SSE). Data was drawn from a
wide range of sources, most frequently from the World
Bank, the UN, and governmental reports. Of the three
independent variables, CCMC and STI are statistically
signifcant with weak to moderate R-square values. The
data shows that homosexual rights increase as CCMC
decreases and as WIOH increases. This suggests that the
more traditional a marriage culture a country has, the less
homosexual rights it will aford its citizens. The more a
countrys women act outside of the homethat is, in the
workforce and political systemthe more homosexual
rights will be protected.
GTTOWER.ORG | 65
ARTICLE
opposite is true; women are older at frst marriage and
childbirth and have more infuence on spouse selection.
Childbearing is often a measure of a persons value
or adulthood. Reixachs study on personhood and pro-
creation highlights the importance of reproductivity to
southeastern European cultures (1998). In these societies,
personhood is defned by fertility. For example, a woman
is not considered a woman except during her childbearing
years. A married couple without children is not consid-
ered a family. The value of adults, then, is dependent upon
their children or ability to have children. Similarly, Bell
argues that marriage is a solution to men seeking rights
to womens reproductivity and a way to defne peoples
place in society (1997). Marriage and social standing are
therefore inextricably linked to reproductivity.
Womens infuence outside the household
Very few studies link homosexual rights to womens in-
fuence outside the household (WIOH), among them Stef-
fens and Wagner (2004) and Herek (1998). WIOH is most
simply defned as the participation of women in civil so-
ciety, the labor force, and/or government. When restricted
to the household, women lack the ability to directly infu-
ence society. Outside the domestic sphere, on the other
hand, women have more opportunities to afect society.
As women have been shown to be more receptive to ho-
mosexual rights than men, womens public infuence can
impact homosexual rights (Stefens and Wagner, 2004;
Herek, 1988).
Employment is one way for women to move outside
the household and gain infuence. Whether women are
able to enter the labor force is based on both the demand
for women, which is based on the amount of female-dom-
inated jobs, and the supply of women, which is based on
factors such as education, marriage age, fertility, and con-
sumption (Petit and Hook, 2005).
Another important factor that increases the womens
infuence is education. Education increases the oppor-
tunities for women to enter the labor market (Cameron,
Dowling, and Worswick, 2001). This connection is stron-
gest among college graduates. Education also acts as an
opportunity for women to become beter informed. Once
educated, women are beter equipped to become political
or other societal actors.
The fnal factor is political participation. Women ac-
tive in politics are able to directly infuence the law. In the
study of three Latin American countries, Schwindt-Bayer
found that women focus on diferent issues than men,
such as family issues, and over time these issues began to
increase in priority to the point where women are no lon-
ger required to focus only on these issues (2006). Another
study found that, while female legislators in the United
States do focus on family and womens issues, over time
they have become more active in traditionally male-domi-
nated issues such as business and economics (Thomas and
Welch, 1991). Overall, the infuence of women is drasti-
cally afected by whether or not they are politically active.
Sex and STI education
This study will also examine the value of sex and sexually
transmited illnesses (STI) education (SSE) and its efect
on the AIDS stigma and how these relate to an increase in
homosexual rights. In previous research on sex education,
several general trends are notable. The frst of those trends
is that sex education teachers feel unsupported by admin-
istration, unclear as to what material needs to be covered,
and uncomfortable discussing sex education with their
students (Pokharel, Kulczycki, and Shakya, 2006). This
is especially evident in schools that are either heavily in-
fuenced by the government or have strong religious ties.
When teachers cannot adequately teach sex education, it
becomes the students responsibility to learn on their own.
Mturi and Hennink used a survey to study how people
learned about sex education; an overwhelming majority
had relied on the media as opposed to sex education pro-
grams (2005). Many felt that sex education programs were
inefective.
Another trend that can be seen in sex education is
the lack of discourse about homosexuality. In the United
States, for example, only ten states have mentioned homo-
sexuality in sex education policy. Of those ten, six suggest
or require that homosexuality be discussed, whereas the
other four states discourage or prohibit the topic (Kirby
and Scales, 1981). What is notable about this is not the fact
ARTICLE
that so few states draw awareness to homosexuality, but
that almost as many states would prefer not to discuss ho-
mosexuality or acknowledge its existence. When homo-
sexuality is excluded from education programs, citizens
are not informed of safe same-sex practices. In addition,
not having the ability to discuss homosexuality can lead to
misconceptions. One of the biggest misconceptions about
homosexuals is the AIDS stigma (Mitra, 2004). Especially
in African, Asian, and Hispanic cultures, AIDS is typically
deemed the homosexual disease. Politicians often em-
ploy anti-gay slogans in AIDS-related policy situations
(White and Carr, 2005).

Focus and Scope
This study will examine the relationships between CCMC,
WIOH, SSE, and homosexual rights. CCMC, WIOH, and
SSE are the independent variables. Homosexual rights is
the dependent variable. This studys hypothesis is that a
decrease in CCMC will lead to an increase in homosexual
rights. Furthermore, an increase in WIOH or SSE will lead
to an increase in homosexual rights. In a culture in which
there is a more traditional CCMC, homosexual rights will
be low. Where people are defned or measured by their
reproductivity, homosexual rights will be low. This is be-
cause homosexual couples do not reproduce biologically
in the traditional sense. In a similar vein, where marriage
is defned by procreation, homosexual rights will be low.
Several studies indicate that women hold a more favor-
able atitude towards homosexuals than men (Stefens
and Wagner, 2004; Herek, 1988). In order for this atitude
to be refected in the public sphere and afect policy, it is
necessary for women to participate in the public sphere.
Womens infuence is frst increased by an increased ac-
cess to education and increased access to the labor force.
As these increase, it becomes easier for women to become
more active in government and afect atitude change
at a national level. Overall, the increase of all three of
these factors leads to an increase in womens infu-
ence, which leads to an increase in homosexual rights.
Countries that provide a comprehensive sex educa-
tion will have a greater level of homosexual rights
than those that have a less comprehensive or no sex
education. A comprehensive sex education program will
discuss homosexuality. By incorporating homosexuality
into the program, common misconceptions regarding ho-
mosexuals will be discussed. This will lead to more gener-
al knowledge and thus a reduction in the bias towards ho-
mosexuals, especially when addressing AIDS. Since AIDS
is such a big issue throughout the world and cultures have
deemed it the homosexual disease, governments have
been reluctant to guarantee homosexual rights.
Methodology
Homosexual rights
The dependent variable of this study is homosexual rights.
This study will focus on two specifc rights most indica-
tive of overall homosexual rights: the right to be homo-
sexual and the right to marriage. While other homosexual
rights exist, such as the right to serve in the armed forces
or the right to adopt children, these are generally much
more rarely recognized. The right to be homosexual, as the
most basic of homosexual rights, and the right to marry,
a higher-level right, create a range that may indicate the
presence of other rights, such as the right to freedom from
discrimination in the workplace.
This study will create an ordinal scale to apply data
collected from the International Lesbian, Gay, Bisexual,
Trans and Intersex Association (ILGA) in 2011. The scale
will quantify homosexual rights based on the legality of
being homosexual (Category A) and the legality of homo-
sexual marriage (Category B). As legal codes in several
countries distinguish the legality of male as opposed to
female homosexuality, Category A has two parts: Part I,
Male to Male and Part II, Female to Female. These catego-
ries are separate but equally weighted. If homosexuality
is illegal in either part, the score for that country is 0. If
it is legal in some areas or the law is unclear, the score
is 0.25. If homosexuality is legal, the score is 0.5. The two
parts are then totaled for a score ranging from 0 to 1. For
Category B, Marriage, there is no distinction between male
and female homosexuality. If marriage is illegal or unrec-
ognized, the score is 0. If the laws difer by area (such as
in the United States), or there is a nationally-recognized
GTTOWER.ORG | 67
ARTICLE
substandard marriage substitute, or a standard substitute
recognized in some areas, or an equal or almost equal sub-
stitute recognized in some areas, the score is 0.5. If there is
a nationally-recognized equal or nearly equal substitute to
marriage, the score is 1. If homosexual marriage is legal,
the score is 2. This score is then divided by 2, to give it the
same weight as the Category A score. After the Category B
score is rescaled, it is added to the Category A score. The
scores range from 0 to 2, with increments of 0.25. 0.00 in-
dicates no homosexual rights; in all of our cases, 0.25 indi-
cates that it is legal to be lesbian but illegal to be gay. 1.00
indicates a medium level of homosexual rights (in all of
our cases, but not necessarily by defnition, it means that it
is legal to be homosexual but homosexual marriage does
not exist). 2.00 indicates that it is legal both to be homo-
sexual and to marry a member of the same sex (Table 1).
The independent variables are CCMC, WIOH, and SSE.
Data for the independent variables is from the years 2001-
2011. The newest data from the time period 2001-2010 was
used; if no data from 2001-2010 was available, 2011 data
was used. CCMC measures include under-fve mortality
rate, fertility rate, adolescent birth rate, ideal number of
children for women, and percent women using contracep-
tion. Under-fve mortality rate, or deaths per 1,000 chil-
dren under the age of fve, was gathered from the World
Health Organization (WHO) and the World Bank. Fertility
rate, or births per woman, was gathered from the World
Bank. Adolescent birth rate (births per 1,000 women aged
15-19) data was gathered from the United Nations Depart-
ment of Economic and Social Afairs (UNESA). Ideal num-
ber of children per women for developing nations from
USAID; for OECD nations, the data was gathered from an
OECD report. However, several countries data were not
available in these reports, so many data points were gath-
ered individually from research papers or governmental
studies. Finally, contraception use was measured by the
percent of women using any contraceptive method, gath-
ered primarily from the UNESA. Again, several countries
data were not available in the primary source; several data
points were therefore gathered from 128 other sources
such as governmental reports (see References: Data Sourc-
es).
This study considered several other measures for
CCMC. The most important were age at frst marriage and
age at frst childbearing. However, data was not available
for a large number of countries. Data was available for
minimum legal age at marriage; however, in many parts
of the world, the minimum legal age is not enforced and
can be circumvented with parental consent. Mean age at
childbearing data was available, but it was not age at frst
childbearing.
Independent Variables
CCMC scores were calculated using Equation (1) to range
Score Identity Marriage
Male to Male Female to Female
0 Illegal Illegal Illegal
0.25 Unclear or legal in some
areas
Unclear or legal in some
areas
Not applicable
0.5 Legal Legal Marriage laws vary depending on area or recognized in some areas
or inferior substitute recognized in some areas or inferior substitute
but nationally recognized or equal/ almost equal substitute recog-
nized in some areas
1 Not applicable Not applicable
2 No law (legal)
Table 1 Dependent variable coding
ARTICLE
from 0 to 100, although the actual scores range from 7.2
(Singapore) to 90.3 (Niger) with a mean of 28.1. Each mea-
sure was divided by the maximum measure in that catego-
ry. For example, Afghanistans infant mortality rate, 103,
was divided by 114, the maximum infant mortality rate
from the dataset. The contraceptives rescaled score was
subtracted from 1, as a higher contraceptive score would
indicate a less traditional CCMC. Finally, an average was
taken of the measures and scaled to the 0-100 scale, with
higher scores indicating a more traditional childbearing,
childrearing, and marriage culture. If any data points were
missing, the average was calculated without that category.
Each country had at least one data point.
(1)
where CCMC is Childbearing, Childrearing, and Marriage
Culture; UMR is Under-5 Mortality Rate; FR is Fertility
Rate; AFR is Adolescent Fertility Rate; INC is Ideal Num-
ber of Children; and CPR is Contraceptive Prevalence
Rate.
WIOH was calculated using three measures: fe-
male enrollment in tertiary education, ratio of female
to male labor force participation rate, and women in
national legislatures (Equation 2). Data was drawn
primarily from World Bank and UN Stats datasets. The
data from these factors was then divided by the maximum
data point from each section in order to create a scale of
0 to 1 for each country in each category. An average of
the three categories was then calculated and the variable
was rescaled to the same scale as CCMC, from 0 to 100. A
higher score indicates more female involvement outside
the household. The scores range from Marshall Islands
(6.8) to Puerto Rico (86.6).
(2)
where WIOH is Womens Infuence Outside the House-
hold, FETE is Enrollment in Tertiary Education, WNPL
is Women in National Parliaments or Legislatures, and
FMLFP is Female to Male Labor Force Participation.
For SSE, an ordinal scale was created based on trends
found in diferent literature. The scale consists of integers
ranging from 0 to 3. A score of 0 indicates that a coun-
try has no evidence of sex education or that government
ofcials have publically spoken against providing sex
education. A score of 1 indicates that a country has some
evidence of sex education, whether it is through schools
or nongovernmental organizations. A score of 2 indicates
that sex education is required by the government or gov-
Score Justifcation Examples
0 No evidence of sex education or sex education is illegal Djibouti, where there is no reputable evidence of sex education
available; Brazil, where the government has banned sex education
material due to homosexual references.
1 Little evidence of sex eduaction or sex education is
provided but considered inadequate or NGOs provide
sex education
Nigeria, where sex education is very recently introduced to the
education system; Italy, where sex education is highly infuenced
by the Catholic Church and therefore not comprehensive; Mozam-
bique, where UNICEF provides literature for children.
2 Government requires sex education or governing edu-
cation body requires sex education
Austria, where the government requires sex education; Hungary,
where the Ministry of Education regulates sex education.
3 Joint efort between government and NGOs to provide
sex education
The Netherlands, where NGOs and the government cooperate to
provide sex education.
Table 2 Sex and STI education coding
GTTOWER.ORG | 69
ARTICLE
erning education body. Finally, a score of 3 indicates a
cooperative efort between governments and nongovern-
mental organizations to provide as much sex education as
possible (Table 2).
In order to create the scale, each country in the data
set was researched individually to determine policies and
regulations regarding sex education. The one factor that
could not be taken into account with this scale is access
to media such as television as well as social media like
Facebook and Twiter. Data was not available on whether
specifc sex education programs discussed homosexuality,
and so this study was unable to take homosexuality edu-
cation into account.
Statistics
This study will use ordinal regression tests with the JMP
software package. This will consist of four diferent tests:
one per each independent variable, comparing said vari-
able to the model, and one to compare all three indepen-
dent variables simultaneously to the model.
Results
The model is statistically signifcant with p < 0.001. The
model has a moderate ft with an R-square value of 0.2676.
All variables except SSE are statistically signifcant (Table
3). WIOH has the highest R-square value, 0.1783. CCMC
follows with an R-square value of 0.1198. SSE has a weak
R-square of 0.0887.
With CCMC signifcant, this model shows that a more
traditional childbearing, childrearing, and marriage cul-
ture leads to weaker homosexual rights. Therefore, the
more traditional a countrys marriage and child culture,
the fewer rights that country recognizes for homosexuals.
With WIOH signifcant, this model shows that a greater
level of womens public infuence leads to more homosex-
ual rights. Therefore, the more women operate outside the
domestic sphere, the more homosexual rights that country
recognizes.
While SSE is not statistically signifcant, it is very close,
with a p-value of 0.0587. Were the p-value to be under 0.05,
the model would show that a higher level of sex and STI
education would be present in countries with a greater
level of homosexual rights.
Discussion
The results of the ordinal regression support the research
hypothesis, demonstrating that there is a relationship be-
tween childbearing, childrearing, and marriage culture;
womens infuence outside the household; and homosex-
ual rights. The more traditional a countrys childbearing,
childrearing, and marriage culture, the lower that coun-
trys level of homosexual rights. The more a countrys fe-
male citizens have infuence outside the domestic sphere,
the higher that countrys level of homosexual rights.
These results lead to several observations. First, the
fact that womens infuence and homosexual rights are
correlated implies that human rights are politically relat-
ed. If a countrys political culture is supportive of equal
rights in general, this is not surprising. This has policy im-
plications for states, NGOs, or individuals that hope to ex-
pand support for homosexual rights: these groups would
be well advised to also support womens rights. Second,
these groups could also address some of the factors of
CCMC. This is not to suggest that any group should at-
tempt to change a countrys culture, but rather that basic
development help, for example work to reduce the infant
mortality rate or provide greater access to contraception,
could in the long term afect a countrys disposition to-
wards homosexual rights. Notably, greater access to con-
traception would afect womens ability to operate outside
the household, as it would give women more control over
how much of their lives they commit to childbearing and
childrearing.
Further research could focus on data gathering. Some
measures have incomplete data, for example ideal number
of children; other measures had so litle data available that
this study could not use them. Some measures were not
Statistic CCMC WIOH SSE
P-value <0.0001 0.0002 0.0587
R-squared 0.1198 0.1783 0.0887
Table 3 Results for each variable
ARTICLE
available for the time period; many European countries,
for example, have no data for contraceptive prevalence
since the 1980s. Mean age at frst marriage or mean age
at frst childbirth are both demographic measures that are
not available for most countries. Furthermore, litle data
on sex education programs exists. When there is data on
the existence of a program, there is usually no data on that
programs contents, which means that abstinence-only
sex education programs and programs that discuss other
methods of preventing pregnancy and STIs are indistin-
guishable.
Another focus for further research could be on ex-
ploring the correlation between diferent types of human
rights. This study found a correlation between WIOH
(which assumes a basic level of womens rights) and ho-
mosexual rights; other studies might explore the right to
religious freedom, free speech, or the rights of various eth-
nicities. An interesting trend is notable in the data on ho-
mosexual rights. In several countries, it is illegal to be gay,
but legal to be lesbian. Further research could investigate
the cause of this discrepancy.
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GTTOWER.ORG | 75
Educators want to give students every opportunity to succeed, even after
graduation. The innovative minds at Verizon have teamed up with some of
the smartest companies around to create solutions that help instructors
and students collaborate, even across great distances.
Because the worlds biggest challenges deserve even bigger solutions.
Solutions for Higher Education: verizon.com/education
Network details & coverage maps at vzw.com. 2013 Verizon Wireless.
TECHNOLOGY TO IMPROVE EDUCATION,
SO STUDENTS CAN GO OUT AND
IMPROVE THE WORLD.
{POWERFUL ANSWERS}
Sinan Liu
1
& Madhavan Swaminathan, PhD
1
I mpr oved s i gnal i nt egr i t y and power
cons umpt i on i n hi gh s peed di gi t al ci r cui t s
Signal integrity is critical to the overall performance of a
device, however numerous factors can degrade signal such
as signal noise and long distance loss. In order to achieve a
good signal quality, it is important to maintain a constant
power supply voltage and minimize fuctuations from
noise. For digital circuits operating at high frequencies,
parasitic inductance is one of the primary sources of
noise that leads to signal degradation. Derived from Far-
aday Law, inductance coupled with a change in current
produces variations in voltage that afect the power sup-
ply voltage. This type of noise is also referred to as Simul-
taneous Switching Noise (SSN). On a printed circuit board
(PCB), nearly all metal components, such as integrated
circuit (IC) package pins, traces, solder balls, wire bonds,
and power ground planes exhibit an intrinsic inductance
which can be considered parasitic. Since it is rather dif-
fcult to reduce the inherent inductance characteristics of
these materials, the best way to improve signal integrity
and reduce noise is to minimize the change in current.
The conventional PCB using power/ground plane is
plagued with SSN. SSN is a result of the coupling between
the signal lines and the power delivery network. This cou-
pling occurs at the discontinuities of the transmission line,
where there is an interruption of the current return path
(Swaminathan et al. 2007). To solve this problem, power
transmission line (PTL) is proposed (Engin et al. 2008).
PTL can not only eliminate the SSN but can also reduce
the cost of fabricating PCBs by replacing the power plane
layer with a transmission line. But without the resistive
paths, dynamic DC drop in power transmission line sche-
matic cannot be avoided (Huh et al. 2009).
1
School of Electrical Engineering, College of Engineering, Georgia Institute of Technology. Correspondence should be addressed to
SL (liusinan1010@gmail.com).
Currently, maintaining signal integrity of digital sys-
tems that are capable of operating at high frequencies
is difcult. In high-speed digital systems, numerous fac-
tors afect and degrade the signal integrity, such as sig-
nal noise, and long distance transmission loss. A criti-
cal signal integrity problem is noise due to the intrinsic
parasitic inductance of the printed circuit board and in-
tegrated circuit package coupled with rapid changes in
current. The noise voltage is defned by inductance and
current change rate. Therefore, if a constant supply cur-
rent can be maintained, the noise voltage can be reduced,
and the signal integrity can be improved. In this paper,
a power reduction encoding scheme is developed to im-
prove signal integrity and reduce the power consump-
tion.
ARTICLE
GTTOWER.ORG | 77
ARTICLE
Constant voltage power transmission line (CV-PTL),
which in summary alters the power delivery method for
ICs on a PCB, is proposed to solve the dynamic DC drop
problem (Telikepalli et al. 2012). As shown in Fig. 1, with
the resistive paths implemented, we are able to select the
resistive path to match the bit-patern, in other words, the
current, to make the voltage level at this node constant for
all time. CV-PTL is able to successfully improve the signal
integrity; however, it noticeably increased the power con-
sumption.
In digital systems, the current varies as the output
switches between high voltage and low voltage (indicated
by bit values of 1 and 0, respectively). Transmiting
a 1 consumes more current, hence more power, than
transmiting a 0. With this in mind, transmiting as few
1s as possible and more 0s, can reduce power con-
sumption and also minimize the change in current to im-
prove signal integrity. Therefore, the purpose of this study
is to develop an encoding scheme to transmit fewer 1s
to reduce the power consumption and improve the signal
integrity. A proposed encoding scheme would facilitate a
reduction in power consumption within CV-PTL systems.
Methods
Power encoding scheme
The algorithm behind the power encoding scheme was de-
signed to target and encode the most power-consuming
states. Based on the input data size, it can be determined
which states to encode. For example, as shown in Fig. 2, it
is a truth table for a 4-bit input. Based on the designed al-
gorithm, respect to 4-bit input, targets are states with three
or more 1s highlighted in yellow. To encode the data,
the scheme actually transmits an extra bit referred to as the
fag bit (Stan et al. 1995; Cheng et al. 2001). For the targeted
states, the fag bit is set to 1 and the complement of the
original input data is transmited. The fag bit also signi-
fes to the receiver which states to decode. For example,
for the most power-consuming states where all four 1s
are transmited, the fag but is set to 1 and the comple-
ment 0000 is transmited. Rather than transmiting four
1s we transmit only one and consuming one-fourth the
power. As shown in Fig. 2, the number of 1s represents
the amount of current that is fowing in the circuit. Since
the variation of the number of 1s is smaller in the en-
coded truth table on the right, the current variation of the
Figure 1 Constant voltage power transmission line system schematic
ARTICLE
encoding scheme is smaller correspondingly.
The schematic, shown in Fig. 3, outlines the combi-
national logic needed to implement the power encoding
scheme for an input size of 4-bit. The implementation is
much more complicated as we increased the number of
input bits, because we need to add more than one fag bit
in order to transmit as few 1s as possible. We decided to
implement the encoding using a feld-programmable gate
array (FPGA). A FPGA contains a matrix of reconfgurable
gate array logic circuitry that, when confgured, is con-
nected in a way that creates a hardware implementation
of a software application. Unlike processors, FPGAs use
dedicated hardware for processing logic and do not have
an operating system. Because the processing paths are
parallel, diferent operations do not have to compete for
the same processing resources. That means speeds can be
very fast, and multiple control loops can run on a single
FPGA device at diferent rates. (Robbins et al. 2010)
Encoding scheme validation
In order to test our scheme, we used a Xilinx FPGA IC on
a PCB. First, with an input clock signal we implemented a
linear feedback shift register (LFSR) which outputs a pseu-
dorandom binary sequence (PRBS) which serves as input
data to our encoding logic implemented with VHDL. From
the encoded output, we produced and measured eye dia-
grams to evaluate our encoding scheme.
Results
Peak-Peak signal jiter
The eye diagram, a method to test the signal integrity,
uses the data rate to trigger an oscilloscope display. Us-
ing this method, we observed the signal waveform from
the receiver. Several system performance measures can be
derived by analyzing the display. The height, width, and
peak-peak (p-p) jiter determines the signal integrity. In
our project, we expect larger width and height and smaller
p-p jiter. Jiter is undesired deviation from the true period-
icity of an assumed periodical signal. Therefore, small p-p
jiter implies high signal integrity. With 4-bit input, we did
a comparison between original output and encoded out-
put from 100MHz to 600MHz. For example, the compari-
sons of eye diagrams at 100MHz and 400MHz are shown
in Fig. 4. At 100MHz, the p-p jiter of encoded output re-
duces to 213.4 ps, compared to the original output at 291.4
ps. At 400MHz, the p-p jiter of encoded output reduces
from 206.65 ps to 126.65 ps. Using the data we observed
from the eye diagram, we made a graph of the reduction
of peak-peak jiter shown in Fig. 5.
Figure 2 Truth table of a 4-bit encoding scheme
Figure 3 Field-programmable gate array programming fowchart
GTTOWER.ORG | 79
ARTICLE
Power consumption
The current consumption can be determined by 1s used
in digital systems. The graph of current consumption is
shown in Fig. 6 representing the comparison between sys-
tem with original input signal and that with encoded in-
put signal. In Fig. 6, we can see that the red curve, which
represents the current with the encoding scheme, has a
smaller swing between the maximum and minimum val-
ue, compared to the blue curve that represents the current
without the encoding scheme. The encoded current is low-
er than the original one at any time spot, indicating that
the implementation with the encoding scheme consumes
less current, thereby reducing the power consumption.
Furthermore, the average power reduction was tested and
calculated with various numbers of input bits. The results
are 21.88% for 4-bit, 19.79% for 6-bit, and 18.26% for 8-bit.
Discussion
The objective of this project is to improve the signal integ-
rity and reduce the power consumption in CV-PTL sys-
tems. An encoding scheme that transmits fewer high volt-
age states is proposed to improve the signal integrity and
reduce the power consumption. According to the mea-
surement, the system with encoding scheme has less SSN,
in other words, has beter signal integrity. Also, its power
consumption is lower than the system without encoding
scheme. It agrees with the initial hypothesis.
CV-PTL is another efective method to improve the
signal integrity. However, its drawback is large power
consumption. Therefore, if this designed encoding scheme
Figure 4 Peak-peak jitter of the output signal. (A) Eye diagram of original output at 100MHz over 9.60 ns with 114 mV amplitude. (B) Eye
diagram of encoded output at 100MHz over 9.72 ns with 123 mV amplitude. (C) Eye diagram of original output at 400MHz over 2.265 ns
with 107 mV amplitude. (D) Eye diagram of encoded output at 400MHz over 2.37 ns with 108 mV amplitude.
ARTICLE
can be integrated with CV-PTL, it can help CV-PTL reduce
its power consumption at the same time improve the sig-
nal integrity.
Although this encoding scheme was successful to
improve the signal integrity and reduce the power con-
sumption, further research is needed on a more advanced
scheme to reach further improvement. A potential prob-
lem of this encoding scheme is that we added an extra bit,
fag bit, to signify to the receiver which states to decode.
However, if an extra bit is added, more drivers are needed
in the digital system, so that extra power would be con-
sumed by the added drivers. Therefore, the power con-
sumption of CV-PTL systems could be further reduced
with a more advanced encoding scheme that can encode
the signal without adding an extra bit.
Acknowledgements
Sponsors: Georgia Tech College of Engineering; Semiconductor Re-
search Corporation; Intel Corporation; Education Alliance
Collaborators: Austin Foote; Di Sheng
Ph.D. mentor: Sang Kyu Kim
Faculty advisor: Madhavan Swaminathan, PhD
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taneous switching noise at reduced power transmission lines for
high-speed signaling, Electrical Performance of Electronic Pack-
aging and Systems (EPEPS), 2012 IEEE 21st Conference on , vol.,
no., pp.29,32, 21-24 Oct. 2012
6. Cheng, W.; Pedram, M., Memory bus encoding for low power:
a tutorial, Quality Electronic Design, 2001 International Sympo-
sium on, 2001
7. Stan, M.; Burleson, W. Bus-invert coding for low-power I/O,
IEEE Trans. Very Large Scale Integr. (VLSI) Syst., vol. 3, pp. 4958,
Mar. 1995.
8. Robbins, R., Advantages of FPGAs, Control Engineering,
Figure 5 Comparison of measured peak-peak jitter between a
system with an original input signal (blue line) and a system with an
encoded input signal (red line). Error bars = standard error.
Figure 6 Comparison of simulated current consumption between
a system with an original input signal (blue line) and a system with
an encoded input signal (red line).
GTTOWER.ORG | 81
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Kiara Cui
1
, Mackenzie Martin
2
, & Paula T. Hammond, PhD
1
Synt hes i s of pol ypept i des f or hydr ogel
s caf f ol ds
Biocompatible hydrogels have a plethora of applications,
such as modeling cellular environments in tissue studies,
acting as a medium for drug and gene delivery, and in-
corporation into products such as wound fller, biosensor
membranes, and contact lenses (Oelker et al. 2012). The
motivation for using synthetic polypeptides as a structur-
al base for hydrogels stems from their ability to success-
fully mimic the extracellular matrix. The extracellular
matrix or ECM can be seen as a complex network of
organic macromolecules such as proteoglycans, fbronec-
tin, and collagen that surrounds the cell. It plays a vital
role in cell function by interacting with extracellular sig-
nals which can ultimately activate transcription of target
genes (Engler et al. 2009). This is depicted in Fig. 1.
This project focuses on the synthesis of two of these bio-
compatible polypeptides, poly(propargyl-L-glutamate),
PPLG, and poly(allyl-L-glutamate), PALG, whose struc-
1
Department of Chemical Engineering, Massachusets Institute of Technology.
2
Department of Chemistry, Massachusets Institute
of Technology. Correspondence should be addressed to KC (kiaracui@mit.edu).
Biocompatible polypeptides are the main structural com-
ponent of hydrogels, which can be used for cell studies
and biocompatible materials such as wound fller. Two
of these synthetic polymers, poly(propargyl-L-gluta-
mate), PPLG, and poly(allyl-L-glutamate), PALG, are of
particular interest due to the accessibility of their pen-
dant alkyne and alkene groups, respectively, for click
chemistry. The atachment of various functionalities to
the polymer backbone allows for mimicry of the extra-
cellular matrix. A general scheme for the traditional or-
ganic synthesis of these polymers has been developed
and shows promise for extended study, further modifca-
tion of properties, and a variety of applications.
ARTICLE
Figure 1 Structure of the ECM showing interaction with extracel-
lular signals and transcription of target genes (Lutolf et al. 2005).
GTTOWER.ORG | 83
tures are shown in Fig. 2. These particular compounds
are of interest due to their low toxicity, biodegradabil-
ity, tunable structures, and well-controlled dimensions
(Engler et al. 2009). Especially important in their ability to
mimic the ECM is the presence of a pendant alkyne and
alkene group in PPLG and PALG, respectively, which are
readily available for click chemistry.
Click reactions were frst popularized by former MIT
professor and Nobel Laureate K. Barry Sharpless (Kolb et
al. 2001) and are known for their simplicity, nearly 100%
efciency of conversion with limited byproducts, and ver-
satility with diferent functional groups. Examples include
the copper-mediated alkyne-azide and thiol-ene reactions
shown in Fig. 3. Pendant alkyne and alkene groups are
especially convenient as handles for ataching functional
groups due to the commercial availability of functional-
ized reagents such as those in Fig. 4.
Like PPLG and its pendant alkyne, PALG and its pen-
dant alkene are also sterically accessible and well-suited
for click chemistry. Functional groups such as alcohols,
aldehydes, amines, and carboxylic acids may be grafted
onto the polypeptide backbone in this manner (Tang et al.
2011). This incredible versatility can be furthered through
a co-polymerization of the propargyl-L-glutamate (PLG)
and allyl-L-glutamate (ALG) monomer to give two difer-
ent handles for the atachment of functionalities.
In addition, several features of these polypeptides
can be adjusted using synthetic methods. An example is
polypeptide secondary structurestif alpha helices ver-
sus fexible random coils. This is of interest since diferent
cell phenotypes such as skin cells and heart cells possess
varying degrees of fexibility. After synthesis of the poly-
peptide, this property will carry through cross-linking and
hydrogel formation to defne the stifness of the fnal hy-
drogel product. The syntheses of PPLG and PALG begin
ARTICLE
Figure 2 Structures of PPLG and PALG. Pendant alkyne and al-
kene groups are highlighted.
Figure 3 Common click reactions. The CuBr-mediated alkyne
azide reaction (a) and the thiol-ene reaction (b).
Figure 4 Commercially available reagents containing azide
groups. These can easily be clicked onto a PPLG backbone.
with glutamic acid, which has two enantiomeric forms.
Using only one enantiomer will result in a stif -helix
structure, while a 1:1 ratio of L- and D-glutamic acid will
disrupt the hydrogen bonding to give a fexible coil (Oelk-
er et al. 2012) (Fig. 5).
Materials & Methods
Reagents
All reagents were purchased from Sigma-Aldrich. Water
as used in the protocol refers to Milli-Q water. Prior to ex-
perimentation, all glassware was rinsed with acetone and
dried under nitrogen fow, unless otherwise noted in the
procedure.
Synthesis of PPLG
The reaction scheme for the synthesis of
poly(propargyl-L-glutamate) as adapted from
Oelker et al. is shown in Scheme 1.
Recrystallization of the starting material
25 g of L-glutamic acid were added to about 200 mL of
Milli-Q water in a 1000 mL Erlenmeyer fask and heated
to 90C with stirring, then fully dissolved using minimal
water for a total volume of 600-800 mL. The fask was cov-
ered with paraflm and placed in the cold room for at least
24 hours. This gave white crystals which were collected in
a Bchner funnel using vacuum fltration, rinsed with cold
water, transferred to a round botom fask, and fully dried
using high vacuum.
ARTICLE
Figure 5 Varying stifness of PPLG and PPDLG hydrogels. Adapted
from Oelker et al.
Scheme 1 Synthesis of PPLG. L-glutamic acid forms an ester link-
age with propargyl alcohol to give propargyl-L-glutamate (a), which
reacts with triphosgene to give an N-carboxyanhydride monomer
(b), which is then polymerized using a primary amine initiator to
form PPLG (c).
GTTOWER.ORG | 85
Formation of ester linkage
The recrystallized L-glutamic acid was weighed and
added to propargyl alcohol in a large round botom fask
(about 30 mL of propargyl alcohol per gram of glutamic
acid). The fask was stoppered and placed in an ice water
bath. An inert argon atmosphere was created via a syringe
needle through the stopper. Once this was removed, 2.15
mL of trimethylsilyl chloride (TMSCl) per gram glutam-
ic acid was added dropwise using a syringe pump over
the period of an hour. Following this, the ice bath was re-
moved and the mixture was allowed to react at 20C with
stirring for 36-48 hours.
Unreacted solids were separated from the fltrate us-
ing gravity fltration. The fltrate was then precipitated
into about 10 times the volume of diethyl ether with stir-
ring at room temperature. The resulting white precipitate
was collected using vacuum fltration and dried using
high vacuum.
Recrystallization of propargyl-L-glutamate
The resulting solid was transferred into a 1000 mL Erlen-
meyer fask. 500 mL of acetonitrile were added, and the
contents of the fask were heated to 45C with stirring.
Minimal N,N-dimethylformamide (DMF) gave complete
dissolution of the solid. After cooling to room tempera-
ture, the fask was covered with paraflm and placed in the
cold room for no more than 24 hours. The resulting white
solid was fltered and dried.
Formation of NCA monomer
0.6 g of triphosgene and 20 mL of ethyl acetate per gram
of recrystallized propargyl-L-glutamate were combined in
a three-neck fask. Using the setup depicted in Fig. 6, the
mixture was reacted under argon with stirring at 80C for
ARTICLE
Figure 6 Set-up used for the formation of the NCA monomer
Scheme 2 Synthesis of PALG. Note the similarity of the scheme to
that of PPLG.
ARTICLE
4-6 hours. The acid trap was continuously monitored to
ensure that it did not become clogged.
Following this, the crude product was fltered to re-
move any solid starting materials and chilled in an
ice water bath. It was then washed with 200 mL of
chilled Milli-Q water, 5% NaHCO3(aq), and saturat-
ed NaCl(aq) in that order using a separatory funnel.
The organic component was collected, dried over
MgSO4(s), and fltered. Any remaining solvent was re-
moved using a rotary evaporator and then high vacuum,
and the resulting monomer was fushed with argon. Un-
less used immediately for polymerization afterwards, the
monomer was stored at -40C no longer than overnight.
Polymerization
The propargyl-L-glutamate monomer was transferred to
Figure 7 Sample NMR spectra for the conversion of L-glutamic acid to allyl-L-glutamate. Peaks may be analyzed and matched to corre-
sponding hydrogen atoms on the molecule (a)-(c), and extent of reaction can be evaluated qualitatively based on the appearance of new
peaks or disappearance of old peaks.
GTTOWER.ORG | 87
ARTICLE
an oven-dried Schlenk fask and combined with 10 mL of
DMF per gram of monomer. 28.5 L of 1-aminoheptane
initiator per gram of monomer were added to the fask us-
ing a microsyringe. The mixture was reacted under argon
for 72 hours at room temperature.
Next, the solvent was removed from the crude using
high vacuum. The product was dissolved in minimal di-
chloromethane and precipitated into 10 times the volume
of diethyl ether with stirring. The resulting precipitate was
fltered and dried, giving the desired PPLG polymer.
Synthesis of PALG
The protocol for the synthesis of poly(allyl-L-glutamate)
is nearly identical to that of poly(propargyl-L-glutamate),
as shown in Scheme 2, with the only signifcant diference
being the substitution of allyl alcohol for propargyl alco-
hol.
Discussion
Safety considerations
The syntheses of PPLG and PALG involve several safety
hazards that should be taken into account when carrying
out the procedure. Due to the air- and water-sensitivity of
the organic reactions, a vacuum-gas manifold or Schlenk
line was used to provide an inert argon atmosphere as well
as remove solvents from fltered products. This apparatus
should be monitored for leaks that may lead to implosion
as well as the formation of explosive liquid oxygen from
the air. Triphosgene, a solid reagent used in the formation
of the N-carboxyanhydride monomer, should be kept in
the hood or in a closed vial at all times as it decomposes
to toxic phosgene gas. Finally, allyl alcohol, which is used
as a reagent and solvent in the synthesis of PALG, is fam-
mable and fatally toxic. All general precautions regarding
personal protective equipment should be taken, and only
those trained to minimize the previously mentioned risks
should perform the experiment.
NMR spectroscopy
Upon completion of each stage of the reaction, a sample
of 0.5 mg or 0.1 mL of product dissolved in 0.6 - 0.7 mL
of deuterated dimethyl sulfoxide (DMSO) was used to
obtain a spectrum by nuclear magnetic resonance (NMR)
spectroscopy. Because the target products are known, this
method is useful for confrming the identity of and detect-
ing any impurities within the sample. By monitoring the
changes in the peaks in the spectra, the approximate ex-
tent of conversion can also be determined. Fig. 7 shows
several sample spectra for the conversion of L-glutamic
acid to allyl-glutamate; a Bruker 400 1H NMR was used
for all samples.
Conclusions and Future Work
Overall, this general synthetic method can be used to form
both poly(propargyl-L-glutamate) and poly(allyl-L-gluta-
mate). These two polypeptides can be incorporated into
hydrogels which serve a wide variety of purposes, includ-
ing biocompatible materials and cell studies. Still, many
Figure 8 Proposed structure of hydrolytically stable PPLG. Notice
the replacement of the ester linkage with the amide bond.
Figure 9 Schematic of a hydrogel library. Adapted from Engler et
al. 2011.
ARTICLE
directions and possibilities for future work remain. For
example, the kinetics of PALG formation may be analyzed
throughout the 72 hour period of polymerization by de-
termining the molecular weight of samples taken at regu-
lar time intervals using gel permeation chromatography
(GPC).
In certain situations such as prolonged cell studies, the
degradation of the ester linkage in PPLG may be undesir-
able. This situation could be remedied by the introduction
of a hydrolytically stable amide linkage (Fig. 8).
Co-polymerization of the propargyl-L-glutamate and
allyl-L-glutamate monomers would provide two diferent
means of atachment for functional groups; various prop-
erties may result from block versus random co-polymer-
ization. Eventually, after synthesizing many variations of
PPLG and PALG, ataching various ECM-mimicking func-
tional groups, and cross-linking the polypeptides to form
hydrogels, a hydrogel library of varying properties could
be created (Fig. 9). Thus, the versatility of these polypep-
tides holds great potential in future biochemical applica-
tions.
Acknowledgements
Many thanks to the Emergent Behaviors of Integrated Cellular Sys-
tems (EBICS), a National Science Foundation Science and Technology
Center, and the MIT Undergraduate Research Opportunities Program
(UROP) for their generous funding, as well as the Institute for Soldier
Nanotechnologies and MIT Department of Chemistry Instrumentation
Facilities (DCIF) for providing workspace and equipment access. Fi-
nally, a big thank you to Prof. Paula Hammond and Mackenzie Martin
for your guidance, expertise, and support.
References
1. A. Oelker, S. Morey, L. Grifth and P. Hammond. (2012). Helix
versus coil polypeptide macromers: gel networks with decoupled
stifness and permeability. Soft Mater, 8, 10887-10895.
2. A. Engler et al. (2009). Highly Efcient Grafting onto a Polypep-
tide Backbone Using Click Chemistry. Angew. Chem. Int. Ed., 48,
9334 9338.
3. Lutolf, M., P., et al. (2005). Nature Biotechnology, 23, 47-55
4. H. C. Kolb, M. G. Finn and K. B. Sharpless (2001). Click Chemis-
try: Diverse Chemical Function from a Few Good Reactions. An-
gewandte Chemie International Edition, 40, 20042021.
5. H. Tang and D. Zhang. (2011). Multi-functionalization of heli-
cal block copoly(a-peptide)s by orthogonal chemistry. Polym.
Chem., 2, 1542
6. A. Engler et al. (2011). The synthetic tuning of clickable pH re-
sponsive cationic polypeptides and block copolypeptides. Soft
Mater , 7, 5627-5637.
GTTOWER.ORG | 89
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