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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 government and industry across the nation and around the globe.
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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 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 GTTOWER.ORG | 3 We ure VentoreLub. We ure pussIonuLe ubouL enLrepreneursIIp. We beIIeve In LIe power oI cusLomer dIscovery. We beIIeve In IIIIIng IoIes In LIe worId, noL mukIng LIem. We beIIeve In InnovuLIon, ILeruLIon, und experIence. We vuIue busIness modeIs, ILeruLIon, und experIence. We vuIue busIness modeIs, noL busIness pIuns. We educuLe, curuLe, und creuLe, duIIy. We serte the students, jccult cnd stcjj oj Georic Tech. We never Luke equILy und our servIces ure uIwuys Iree. We ure VentoreLub. GoL un Ideu Ior u sLurLup? Contuct os. venLureIub.guLecI.edu 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 Georgia Institute of Technology 353 Ferst Drive, Suite 137 Atlanta, GA 30332-0290 Email: editor@gtower.org GTTOWER.ORG | 5 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 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 BI OMEDI CAL ENGI NEERI NG Delineation of cell-based therapies to treat insulin- dependent diabetes Thuy Le & Athanassios Sambanis, PhD 32 BI OMEDI CAL ENGI NEERI NG Chronically elevating bursting results in distinct homeostatic changes of cultured neuronal network activity Rachel Candace Law & Steve Poter, PhD 40 DI SPATCH BI OMEDI CAL ENGI NEERI NG 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 10 | The Tower | Volume VI, Issue I 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 Atlanta, GA 30332-0290 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. 14 | The Tower | Volume VI, Issue I 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 16 | The Tower | Volume VI, Issue I 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 18 | The Tower | Volume VI, Issue I 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 20 | The Tower | Volume VI, Issue I 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 24 | The Tower | Volume VI, Issue I (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 26 | The Tower | Volume VI, Issue I 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 28 | The Tower | Volume VI, Issue I 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. 30 | The Tower | Volume VI, Issue I 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 32 | The Tower | Volume VI, Issue I 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 Wallace H. Coulter Department of Biomedical Engineering, College of Engineering, Georgia Institute of Technology. 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 34 | The Tower | Volume VI, Issue I 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 Wallace H. Coulter Department of Biomedical Engineering, College of Engineering, Georgia Institute of Technology. 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 36 | The Tower | Volume VI, Issue I 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 38 | The Tower | Volume VI, Issue I 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. 16. Mina: A Sensorimotor Robotic Orthosis for Mobility Assistance. (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 during walking. Paper presented at the Robotics and Automation, 2004. Proceedings. ICRA04. 2004 IEEE International Conference. 19. Quintero, H. A., Farris, R. J., & Goldfarb, M. (2011). Control and implementation of a powered lower limb orthosis to aid walking in paraplegic individuals. Paper presented at the Rehabilitation Ro- botics (ICORR), 2011 IEEE International Conference. 20. Rahman, T., Sample, W., Jayakumar, S., King, M. M., Wee, J. Y., Se- liktar, R., Clark, A. (2006). Passive exoskeletons for assisting limb movement. Journal of rehabilitation research and development, 43(5), 583. PERSPECTIVE GTTOWER.ORG | 39 21. Rex Bionics. Retrieved 7/08/2013, 2013, from htp://www.rexbion- ics.com/ 22. Strausser, K. A., & Kazerooni, H. (2011). The development and test- ing of a Human Machine Interface for a mobile medical exoskele- ton. Paper presented at the Intelligent Robots and Systems (IROS), 2011 IEEE/RSJ International Conference on. 23. Tsukahara, A., Hasegawa, Y., & Sankai, Y. (2009). Standing-up mo- tion support for paraplegic patient with Robot Suit HAL. Paper presented at the Rehabilitation Robotics, 2009. ICORR 2009. IEEE International Conference. 24. Valiente, A. (2005). Design of a quasi-passive parallel leg exoskel- eton to augment load carrying for walking: DTIC Document. 25. Van Der Kooij, H., Veneman, J., & Ekkelenkamp, R. (2006). Design of a compliantly actuated exo-skeleton for an impedance controlled gait trainer robot. Paper presented at the Engineering in Medicine and Biology Society, 2006. EMBS06. 28th Annual International Conference of the IEEE. 26. Van Asseldonk, E. H., Veneman, J. F., Ekkelenkamp, R., Buurke, J. H., Van der Helm, F. C., & van der Kooij, H. (2008). The efects on kinematics and muscle activity of walking in a robotic gait trainer during zero-force control. Neural Systems and Rehabilitation En- gineering, IEEE Transactions , 16(4), 360-370. 27. Walsh, C. J. (2006). Biomimetic design of an under-actuated leg exoskeleton for load-carrying augmentation: DTIC Document. 28. Walsh, C. J., Endo, K., & Herr, H. (2007). A quasi-passive leg exo- skeleton for load-carrying augmentation. International Journal of Humanoid Robotics, 4(03), 487-506. PERSPECTIVE 40 | The Tower | Volume VI, Issue I 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. 42 | The Tower | Volume VI, Issue I 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) 44 | The Tower | Volume VI, Issue I 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
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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
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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 48 | The Tower | Volume VI, Issue I 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 50 | The Tower | Volume VI, Issue I 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 52 | The Tower | Volume VI, Issue I 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 54 | The Tower | Volume VI, Issue I 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. 56 | The Tower | Volume VI, Issue I 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. 58 | The Tower | Volume VI, Issue I 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). 60 | The Tower | Volume VI, Issue I 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). 62 | The Tower | Volume VI, Issue I 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). 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International migrant stock (% of popula- tion). Retrieved from The World Bank: Working for a World Free of Poverty: htp://data.worldbank.org/indicator/SM.POP.TOTL.ZS 21. The World Bank. (2013). International Migrant Stock, Total. Re- trieved March 10, 2013, from htp://data.worldbank.org/indicator/ SM.POP.TOTL 22. The World Bank. (2013). Net Migration. doi:htp://data.worldbank. org/indicator/SM.POP.NETM 23. The World Bank Group. (2013). Unemployment, total (% of total la- bor force). Retrieved March 21, 2013, from htp://data.worldbank. org/indicator/SL.UEM.TOTL.ZS 24. Transatlantic Trends. (2011). Immigration: Key Findings. German Marshall Fund, Compagnia di San Paolo, Barrow Cadbury, Fun- dacion BVA. 25. United Kingdom Visa Bureau. (2011, April 6). UK Immigration cap comes into force. United Kingdom. Retrieved February 7th, 2013, from htp://www.visabureau.com/uk/news/06-04-11/uk-immigra- tion-cap-comes-into-force.aspx 26. Workpermit.com. (2012, November 23). UK announces permanent skilled immigration cap: Tier 1 for the select few and an overall reduction in immigration. Retrieved March 18, 2013, from htp:// www.workpermit.com/news/2010-11-23/uk/government-an- nounces-skilled-immigration-cap-tier1-select-few.htm 27. Zappi, S. (2003). French Government Revives Assimilation Policy. Retrieved March 10, 2013, from htp://www.migrationinformation. org/feature/display.cfm?ID=165 64 | The Tower | Volume VI, Issue I 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 66 | The Tower | Volume VI, Issue I 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 68 | The Tower | Volume VI, Issue I 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 70 | The Tower | Volume VI, Issue I 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. References 1. Bell, Duran. Defning Marriage and Legitimacy. Current An- thropology 38.2 (1997): 237-253 2. Cameron, Lisa A., J. Malcolm Dowling, and Christopher Woswick. Education and Labor Market Participation of Women in Asia: Ev- idence from Five Countries. Economic Development and Cultural Change 49.3 (2001): 459-477 3. Carr, Robert, and Ruth White. Homosexuality and HIV/AIDS stigma in Jamaica. 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Melles, Meheret. Youth Reproductive and Sexual Health in Bo- tswana . Advocates for Youth, Apr 2009. Web. 15 Dec 2012. htp:// www.advocatesforyouth.org/publications/1335?task=view GTTOWER.ORG | 73 ARTICLE 71. Melles, Mimi. Reproductive and Sexual Health among Ethi- opias Youth. Advocates for Youth. Advocates for Youth , n.d. Web. 10 Dec 2012. htp://www.advocatesforyouth.org/ publications/420?task=view 72. Ming, Lim Sheng. Breaking taboos: Sex education in schools. . The Brunei Times, 23 May 2007. Web. 15 Dec 2012. htp://www. bt.com.bn/classifcation/opinion/2007/05/23/breaking_taboos_sex_ education_in_schools 73. Mishtal, Joanna Z. Understanding Low Fertility in Poland: De- mographic Consequences of Gendered Discrimination in Employ- ment and Postsocialist Neoliberal Restructuring. Demographic Research 21 (2009): 599-626 74. Mitchell, Kate. Bringing Sex Education to Burundis Youth Through Radio. . Maternal Health Task Force, 04 Apr 2012. Web. 15 Dec 2012. htp://maternalhealthtaskforce.org/discuss/ wpblog/2012/04/04/bringing-sex-education-to- burundis-youth- through-radio/ 75. Moghtader, Michelle. Sex education in the Islamic Republic of Iran. CNN World . N.p., 8 2011. Web. 10 Dec 2012. htp://glo- balpublicsquare.blogs.cnn.com/2011/09/08/sex-education-in-the- islamic-republic-of-iran/ 76. Monaco. Countries in Figures--2011. N.p.: United Nations Eco- nomic Commission for Europe, 2011. N. pag. Print. 77. Namibia. Project Hope. Project Hope . Web. 10 Dec 2012. htp:// www.projecthope.org/where-we-work/africa/namibia.html 78. Nauru. Nauru Demographic and Health Survey. N.p.: n.p., 2007. Print. 79. New sex education manual in two months. The Jamaica Observ- er . N.p., 22 2012. Web. 15 Dec 2012. htp://www.jamaicaobserver. com/news/New-sex-education-manual-in-two-months 80. NIGER: Reinforcing sex education in high schools. IRIN News. N.p., 12 2009. 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Russian Federation: from the First to Second Demographic Transition. Demographic Research 19 (2008): 907- 72. Print. 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 78 | The Tower | Volume VI, Issue I 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. 80 | The Tower | Volume VI, Issue I 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 References 1. Swaminathan, M.; Chung, D.; Grivet-Talocia, S.; Bharath, K.; Lad- dha, V.; Xie, J., Designing and Modeling for Power Integrity, IEEE Transactions on Electromagnetic Compatibility. vol. 52, no. 2, May 2010, pp.288-310. 2. Swaminathan, M; Engin, A.E., Power Integrity Modeling and Design for Semiconductor and Systems, Englewood Clifs, NJ: Prentice-Hall, 2007. 3. Engin, A.E.; Swaminathan, M., Power Transmission Lines: A New Interconnect Design to Eliminate Simultaneous Switching Noise, in Proc. Electron. Compon. Technol. Conf., May 2008, pp. 1139 1143. 4. Huh, S.; Chung, D.; Swaminathan, M., Achieving near zero si- multaneous switching noise power delivery networks by eliminat- ing power planes and using constant current power transmission lines, in Proc. Electr. Perform. Electron. Packag., Oct. 2009, pp. 1720. 5. Telikpelli, S.; Swaminathan, M.; Keezer, D., Minimizing simul- 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). 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GEORGIA JET 530 Brisco Boulevard Lawrenceville, GA 30046 770-513-0180 www.gajet.com 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. 84 | The Tower | Volume VI, Issue I 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. 86 | The Tower | Volume VI, Issue I 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. 88 | The Tower | Volume VI, Issue I 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 Activ. Fee: $36/line. Credit approval req. Early Termination Fee (sprint.com/etf): After 14 days, up to $350/line. Individual-liable Discount: Available for eligible company or org. employees or employees of govt agencies participating in the discount program. Discounts subject to change according to the companys or agencys agreement with Sprint and are available upon request for monthly svc charges on select plans. No discounts apply to second lines, Add-A-Phone lines or add-ons $29.99 or less. 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