2009 Science Horizons Projects

Stoyana Alexandrova

(Mentor: Dr. Usheva-Simidjiyska, Beth Israel Deaconess Medical Center)

Regina Kukola

(Mentor: Dr. Melissa Murphy, University of Wyoming)

Research Summary:  Determination of an individuals’ sex from skeletal remains has applications in both archaeological research to better understand population dynamics and forensic investigations to identify deceased individuals (Frutos, 2004). While the most accurate method of sex determination is visual assessment of non-metric sexually dimorphic traits of the crania and pelvis (Buikstra & Ubelaker, 1994), frequently, preservation of skeletal materials impedes the practical application of such methods (van Vark & Schaafsma, 1992).  When the pelvis and/or crania are unavailable, postcranial metrics of long bones can be used to determine sex when regression equations have been previously calculated (Vark & Schaafsma). Osteometric variability of populations from different geographical locations (Iscan et al, 1998) and time periods (Buikstra & Ubelaker, 1994), necessitates unique values and equations for each population under study.

    I spent this past summer in Peru analyzing the skeletal remains of costal archaeological Peruvian populations. My mentor, Dr. Melissa Murphy, has provided me access to data she, along with other student researchers, collected from 1999-2006 as part of the Purucho-Huaquerones Bioarchaoelogical Project. Using this data, I was able to run statistical analyses that allowed me to create equations for estimating sex. I found that the equations that I created were more accurate in assigning sex in the Purucho-Huaquerones population than equations that were derived from Modern Thai, Chinese, Japanese, European, African, and Guatemalan populations.

    It is interesting to note that the rural Guatemalan population has a much less skewed predictive power compared to the predictive power of other populations’ formulae. Due to the fact that the Guatemalan population is the closest geographically, one could suggest that possible gene flow between past populations could be responsible for this similarity in sexual dimorphism. However, the difference could also be attributed to the rural nature of the Guatemalan population that could place health or nutritional constraints, that aren’t present in populations residing more developed areas. Further investigation would be required to determine the roles of genetics and the environment as they relate to the similarity of sexual dimorphism in modern rural Guatemalan and archaeological costal Peruvian populations.  

    In addition to analyzing the Purucho-Huaquerones data, this summer I was also able to collect data of my own from another contemporaneous Peruvian costal population, and a colonial Peruvian costal population. The next steps in my research will to be to test the accuracy of the formulas developed from the Purucho-Huaquerones cemetery on these populations. High levels of accuracy across these populations will suggest a broad applicability of the sex determination formula I initially developed. Varying degrees of accuracy will open up new channels of cultural and scientific inquiry as to why varying degrees of sexual dimorphism may exist across geographic locations in time in past Peruvian populations.

Madison Schaffer

(Mentor: Dr. James S. Diana, University of Michigan)

Research Summary:  When looking at a species' range, populations of animals are often divided into "core" and "peripheral" sections. Although these groups are members of the same species, they may face very different environments, leading to different selective pressures. Therefore, core and peripheral populations may show differences in life history strategy, morphology, and genetics.

Lisa Lamprou

(Mentor: Dr. Deborah Kim; University of Pennsylvania)

Research Summary:The summer of '09 was not simply memorable, but a season of great personal growth for me.  It was the quintessential intern experience.  Having the opportunity to work behind-the-scenes in a major world-class hospital, I believe I developed a profound understanding of the medical profession, how medical research is conducted at the clinical level, and at the same time, picked up valuable tips in the art of science writing.  Equally important, I also learned a great deal about myself. I went into this fellowship with the hope that it would enhance my resume for medical school admission should I chose to pursue a career in medicine. Now, ten weeks later, I realize that being a physician may not be for me; not because I am intellectually or physically unable to take on the rigors of medical school, but because I may not have the emotional discipline that in my view is required.
 
I was very fortunate in this fellowship because my mentor, Dr. Deborah Kim, has proved to be one of the most competent and professionally impressive persons I have come to know. With her selfless guidance, support and direction, I was able to learn and grow throughout the past two months.  Dr. Kim helped me to learn about myself through the projects she assigned me and by allowing me to follow her in her daily routine in the University of Pennsylvania Hospital where she is an attending psychiatrist.
 
I would arrive at the hospital between 0845 and 0915 daily.  The first order of the day was rounds during which Dr. Kim and the other attending psychiatrists, fellows, residents and medical students met to discuss each patient that required a consultation that day. Once the patients needing attention were identified, the physicians and other support persons were grouped into teams and assigned to particular patients.  We would set off walking from one wing of the hospital to the other visiting the patients. These morning sessions gave me a valuable insight into what it was like to work in a hospital. Many of the patients were distressed, and for some, it was clear that they were not going to get better.  For me, this was the hardest part of the whole experience. What I learned from those morning rounds was that in order to cope with the emotional burden of being a physician, one must be able to separate her personal life from what she witnesses and has to deal with at the hospital. This proved difficult for me. I discovered that I was unable to erase from my mind many of the patient faces I saw during my workday once I left the hospital. I worried about the patients we visited and could not help thinking about their likely fates.
 
Morning rounds took place daily except for Wednesdays, the day of the week that Dr. Kim had clinical consultations from 0900 – 1200. These consultation sessions were my favorites. The were held in the 'Maternal Fetal Medicine' section of the hospital. The majority of patients there were either pregnant women, women who had given birth in the past six months, or women who wanted to become pregnant. What these women all had in common was that they suffered from mood disorders – primarily anxiety and depression. Dr. Kim allowed me to sit in on these sessions and I observed how capably she interacted with these patients, effortlessly putting them at ease by addressing their concerns and prescribing treatments where necessary. She firmly stands by the notion that a healthy mother -- not just physically but mentally as well -- is more likely to have a healthy baby. Dr. Kim strongly supports the idea that mothers that require medication to treat their mood disorders should not abandon such treatment once they became pregnant; unfortunately many do because they feel it may harm the fetus. A specialist in her field of high-risk pregnancy -- with the risk being mood disorders and their consequences – Dr. Kim encouraged patients to continue with treatment plans and in most cases, convinced them that the benefits by far exceeded the small risks involved.  This was a novel concept for me as I had the impression that all medications should be banned during pregnancy.  To observe a professional weighing the risks and recommending otherwise was an eye-opener.
 
In addition to the Wednesday morning clinic, Dr. Kim was also involved in a clinic she ran on Monday afternoons from 1300 – 1730. This clinic was very different from the first in that these patients were not always pregnant women, but people of both genders requiring psychiatric attention. At this clinic session, all patients were seen first by the residents.  Afterwards, the attending physician would come in to make sure that the session went well and that any changes in medication recommended by the residents were appropriate. During these clinics it was extremely interesting to observe the professional relationship that unfolded between the residents and the patient, the residents and Dr. Kim, and finally between Dr. Kim and the patients. I was given the opportunity to observe Dr. Kim guiding her residents to arrive at better treatments or solutions for each patient.  I watched as Dr. Kim mothered the patients that needed mothering, set boundaries for the patients that did not have any, and organized the thoughts of patients who came in providing mixed medical histories.  These sessions were clearly valuable for the future physicians.  I recall Dr. Kim discussing with one of the residents the issue of inadvertently coming across a patient outside the clinic.  The resident did not feel comfortable with the idea. I had never considered the possible problem that would arise after discussing with a patient his or her personal life in great detail and then meeting the patient outside of a medical setting.
 
 
Dr. Kim is currently investigating an exciting and novel research project dealing with the use of transcranial magnetic stimulation (TMS) to alleviate the symptoms of depression in pregnant women. If proven harmless for the fetus, it would provide an alternate treatment option for women, who are reluctant to take anti-depressant drugs for whatever reason. These women are currently not only unprotected from antenatal depression during pregnancy, but are also likely to develop postpartum depression, a condition that would make it more difficult to become effective mothers.  TMS is an FDA-approved somatic, non-pharmacological treatment for depression in adults.  It works and Dr. Kim's pilot study to test safety and efficacy during pregnancy could revolutionize the treatment of antenatal depression.

Many women are reluctant to undergo TMS because it is a relatively unknown treatment and fear that it could harm them. One of the tasks I was given by Dr. Kim was to survey prospective candidates and try to recruit them for treatment if they passed certain criteria for selection. I was given a project of scripting and directing a ten-minute video presentation for potential candidates educating them about TMS and what the treatment entailed. It involved a great deal of hard work but it paid great dividends in the satisfaction I felt after it was successfully completed.  It also made me feel as if I had made a positive contribution to the treatment of those unfortunate women who suffer from major depression during pregnancy and putting both themselves and their future children at risk.  

Another project I as given involved facilitating a blood draw from patients before and after they received transcranial magnetic stimulation. This blood sample would be used to assess their brain derived neurotropic factor levels (BDNF), what is believed to be an important factor in depression. With respect to BDNF I was also asked to write a scientific review on what is known about it thus far and what its potential link to antenatal depression could be. This scientific review will hopefully be published in a journal upon its completion. I am proud of the work I put in to all of my projects this summer and I feel as though I am ready now to make an informed decision about my future either as an M.D. or not.
 

Yang Gao

(Mentor: Dr. Georege Amato; American Museum of Natural History, New York)

Brie Stark

(Mentor:  Dr. Paul Grobstein, Bryn Mawr College)

Research Summary: I interned in the summer institutes with K-12 teachers, sponsored by Howard Hughes Medical Institute.  The goal of my summer research was to participate in and facilitate discussion, form relationships and develop new ideas in relation to the brain, education, mental health and inquiry with K-12 teachers in both the Brain and Behavior Institute, lead by Paul Grobstein, and the Inquiry Institute, lead by Wilfred Franklin.  I will summarize these institutes and offer conclusions and points of discussion for the future.

I was both a facilitator and an active participant in discussion during these institutes.  I took part in the daily blogging, as well as in the discussion of curriculum projects and open-ended projects developed for both institutes.  I helped facilitate the use of Serendip as an educator about the usage of the website, the HTML and the formatting, as well as taught side-programs like Windows Movie Maker and Excel. I maintained an ongoing synopsis blog about my experiences throughout the entire internship, which can be found at http://serendip.brynmawr.edu/exchange/bstark.

The Brain and Behavior Institute focused on facilitating emergent-oriented discussion revolving around understanding the nervous system and the brain and how to apply that understanding to the process of education. I helped to create the afternoon schedule for the participants.  My partner and I researched articles and formulated tasks for small groups to undertake and discuss.  We emphasized a new topic daily, so as to increase the knowledge of the participants on relevant behavior or brain oriented subjects.  These topics included neurodiversity, implications of the web, emergent pedagogy and the importance of web creation for both teachers and students. The participants of the course were asked to complete an open-ended project on Serendip that explored a realm that they found interesting, shared several websites or sources for further information and explained the way their ideas about this subject had changed over the course of the institute.  I created a model for approaching this concept.

The Inquiry Institute offered an environment for teachers to discuss and experience the concept of inquiry-based education.  The concept of inquiry was not given a concrete definition, and therefore, the participants created their own definition and method of implementing inquiry in the classroom. Fellow teachers then presented an open-ended lesson to the participants, an example being a lesson on electricity using circuits and pre-made vehicles.  These lessons were then critically discussed and apt to be changed and implemented by the participants according to their grade-levels.  

While observing these institutes, I drew several conclusions.  
 

Globally, I saw a slow shift of interest start to generate itself as the two weeks of the Brain and Behavior Institute progressed: in the first week, there was a lot of emphasis on personal contributions (such as how teachers had implemented discussion topics in their respective classrooms and their own personal experiences).  However, as the second week arrived, emphasis on personal interest started to decrease and there was a lot more discussion about universal culture, learning styles of students and how to assess the student in order to encompass these ideas.  

I learned, through my observations and participation in discussions, that the greatest environment of learning spawns from a willingness to put oneself into discussion without qualms: to socially interact with the other participants in an emergent fashion, and essentially to feel uncomfortable though content to learn something new.  When there was a lack of participation in the discussion, the discussion often became one-sided, lacked depth and lost its appeal to participants.  Another key development made by the institute was the realization, by many participants, that discussion should foster development and learning and is not a word synonymous with inciting anger or hostility.  Questioning and discussing are parts of the learning process.
I, like many of the participants, came to the institute expecting a more concrete definition of what ‘inquiry’ entailed.  However, as the weeks progressed, we all found that ‘inquiry’ did not have the solid definition that we had been expecting.  Many were disconcerted with the idea while many took the idea as a comforting.  Nonetheless, we did settle into the tone that there was no concrete definition for inquiry: that inquiry could be guided or unguided; have or not have overarching principles and that the teachers all had very subjective experiences with implementing these ideas in the classroom.  I personally found that the definition of inquiry is subjective to the teacher and to the student and must be explored on many levels. Inquiry has an entirely different meaning to the teacher because the teacher often has a pre-developed idea that they would like to explore.  The student is focused on the discovery of ideas that interest them on a personal level.

I would offer these following suggestions in order to further explore the above conclusions for future institutes:
I would like to incorporate more administrative figures into these institutes, as teachers mentioned problems with curriculum and school policy.  This way, we incorporate more of the whole system.  

It would, perhaps, be a valuable contribution to spend more time on deciphering the usage of the Web in education, as there were mixed opinions on the subject concerning such things as privacy, necessity and textbooks.  

I felt that a common sentiment from the institutes, and one that I adhere to, is that learning does not end when formal schooling ends, but rather, that education is a lifelong process.  I questioned, what exactly is the role of the teacher in this lifelong learning concept?  Should they prepare the student for what they will probably experience or teach them to question and take advantage of more opportunities?  

In all, I felt that this internship has given me a more global viewpoint of education and its many approaches, as well as connections with diverse behavior and learning styles.  I learned to express myself well through blogs and in person on a variety of subjects.  This opportunity helped me formulate several career paths of interest through exploration with many professionals in the field of education, biology and psychology.
 

Emily Lovejoy

(Mentor: Dr. Paul Grobstein, Bryn Mawr College)

Research Summary: This summer, I participated in the summer institutes for K-12 teachers.  The summer institutes bring together precollege and college educators to discuss ways to enhance science and mathematics education.  The summer institutes teach educators how to make use of classroom diversity, how to explore the idea of a discovery-based approach to education, and they facilitate collaborations between K-12 teachers and university educators.  The institutes aid educators in making science accessible to everyone.  Additionally, they help educators create a style of teaching that encourages students to understand material in a context that relates it to their personal interests and uses hands-on activities to allow for further exploration. Throughout the institutes, participants were required to actively participate in the discussions, and additionally post their thoughts on an online forum (http://serendip.brynmawr.edu/exchange/).  Lastly, they were to develop an open-ended transactional educational experience to share with the group.

I explored the relationships among mental health, science education, and the brain by pursuing long-standing interests of my own in the mental health area and connecting them to contemporary thinking about the brain and about education.  I expected these interactions would help me to develop new ways to think about the intersections of research on the brain, education, and mental health.

During the summer institutes, I facilitated discussions and developed new relationships and ideas with teachers.  The institutes gave me a broader perspective and viewpoint on education.  I learned a lot about different learning styles and human neurodiversity.  I blogged regularly about my experiences this summer, which can be found at http://serendip.brynmawr.edu/exchange/node/4481.  After my experience this summer, I have thought more about what I want to do in the future and am interested in exploring careers that combine education and psychology.

In the future, the inquiry science and brain and behavior institutes may be combined into one, 3 week institute.  I think the team teaching aspect will strengthen the program by providing different viewpoints and teaching styles that will create an even more dynamic discussion.

The summer institutes allowed educators to share their perspectives on how to enhance math and science education.  The participants received a stipend and development grant at the end of the institutes to further their classroom curricula.  I found the institutes to be extremely helpful in providing new perspectives for all participants.  Without the support of the Howard Hughes Medical Institute, none of this would have been possible.

Grace Loudon

(Mentor: Dr. Erica A. Golemis, Fox Chase Cancer Center)

Research Summary: My summer research experience at Fox Chase Cancer center was excellent! I worked in the Golemis lab under my mentor Dr. Olga Plotnikova. Together we worked on a Polycystic Kidney Disease project. After training me in various techniques, Olga put me in charge of most all of the experiments. I assisted in harvesting cystic kidneys from the pups, preparing protein samples, running gels, managing cell culture, immunofluoresce staining, counting cilia and centrosomes, cilia disassembly, cell cycle analysis, and quantifying data in excel as well as quantifying western blot results through Photoshop and excel. After gaining confidence and independence, I was able to repeat these experiments to confirm my results.

This experience has truly changed my prospective of science. I now understand how huge the big picture can be.   Although I have found lab experiences in Biology and Chemistry at Bryn Mawr to be helpful in understanding the concepts taught in class, working in a full time lab has brought me to a new level of understanding. Working in the Golemis lab for 10 weeks gave me the chance to see the entire process of our PKD experiments. Being able to harvest the cystic kidneys and prepare protein samples and cell cultures from these tissues enabled me to fully appreciate the results from western blots and IF staining because I understood the entire process.

Although I am on the pre-med track and want to continue on to medical school, I am most definitely interested in academic medicine after my experience at Fox Chase. After talking with a BMC alum in the oncology department, I have realized that is possible to work in medicine and collaborate with labs on research.  This prospect is very exciting to me, as I never realized it was possible to combine clinical and laboratory research in this way.

Kelsey Lynch 

(Mentor: Dr. Eric Selker, Institute of Molecular Biology, University of Oregon)

Research Summary:  I conducted my summer research project in a molecular biology laboratory at the University of Oregon headed by Dr. Eric Selker, and under the direction of Dr. Zack Lewis, a post-doctoral fellow. The Selker lab conducts research on DNA methylation and its relationship to heterochromatin formation and maintenance in the filamentous fungi Neurospora crassa. The project that I worked on focused on testing the possible relationship of a single protein (the histone variant H2A.Z) and the recently discovered protein complex that directs methylation of histone 3 in Neurospora (histone 3 methylation ultimately resulting in DNA methylation in this species, as for many others). Throughout the project I learned an array of molecular bio lab techniques. Most of my work required Western and Southern blotting, but I also performed a co-immunoprecipitation experiment, performed several genetic transformations (including a quelling transformation, which is essentially RNA interference), and created an H2A.Z knockdown strain using a construct I’d “built” via PCR.

 Unfortunately, the project that I worked on was a bit frustrating; it turned out that the preliminary results from which the project was designed were falsely positive for DNA methylation due to a chromosomal rearrangement (which was not totally unexpected, as the mutants I was working with lacked genes that are important for maintaining the structural integrity of chromosomes). Though most of my work was invalidated by this turn of events, I did make a contribution to my lab (my H2A.Z knockdown constructs and FLAG-tagged H2A.Z strains will be used for experiments in the future). I learned an incredibly important lesson about research: lab science is a lot of work, and sometimes elements beyond your control can adversely affect the most thoughtful and well-designed experiment.

I very much enjoyed the lab atmosphere, and my discovery that the self-directed, self-disciplined nature of academic research suits me well. Learning the “society” of science through my lab colleagues, talking about their educational decisions, the politics of publishing, teaching, basically getting a more intimate view of the “everyday life” for an academic researched was fascinating, and made me think a lot about what I want out of my career in science as well as my future graduate school. This fellowship was also invaluable for me in terms of analyzing what science means to me personally, the importance of science in modern society, and the crucial, but often-neglected interface between scientific research and the general public. While my actual research project may have not been the most conventionally “successful” endeavor, I gained so much from the opportunity to spend time in the research community and spend time in serious introspection about my future in the world of science.

Emily Levine

(Mentor: Dr. Clint Makino, Massachusetts Eye and Ear Infirmary
Howe Laboratory, Harvard Medical School)

Research Summary: Our bodies employ a wide variety of G-protein coupled receptors (GPCRs) to translate outside information via specific ligands into inside signal transduction pathways that ultimately lead to a cellular response. Often, GPCRs have additional, allosteric binding sites that attract other ligands to affect its activity. Genetic mutations in systems involving GPCRs can cause problems in the way that messages from the outside world are relayed to the body. Our visual pigment rhodopsin is a GPCR made up of the protein opsin and its ligand 11-cis-retinal that acts as an inverse agonist to rhodopsin (or, “locks” it in its inactive formation). This summer, I worked with Sadaharu Miyazono in Clint Makino’s Lab at the Mass. Eye and Ear Infirmary to determine whether rhodopsin is subject to allosteric modulation. We hoped that our research would ultimately find therapy for retinal disorders that stem from genetic mutations in rhodopsin.

            I spent the first few weeks learning about the visual transduction cascade and navigating single cell recording. The visual transduction cascade is a great example of how a signal from the outside world (in this case light) becomes translated into a message our brains can understand. Knowing this signal transduction pathway thoroughly allowed me to postulate reasons for various results during our experiments as well as to think about what to do for each consequent experiment. The multitude of steps in single-cell recording took me a lot longer to master, and I felt very rewarded when I was finally able to run an experiment on my own towards the end of the summer. In short, we used a suction electrode to record the electrical activity of single rods and cones, which measures changes in the photoresponse produced by the varying test drugs under both dark-adapted (rhodopsin) and partial bleached conditions (“free” opsin and rhodopsin). The membrane currents were filtered at 30 Hz and digitized at 400 Hz onto an oscilloscope (to compare responses during the experiment) and onto the computer program Pulse 8.07 (for data analysis), among other digital resources.

We had a list of 12 chemicals from a preliminary biochemical screen that determined these drugs affected opsin’s activity. We wanted to test these compounds in vivo, or in a cell system. If a compound affects opsin’s activity in a cell system, it may likely affect opsin’s activity in an animal and could be used pharmaceutically. Sadaharu and I started off testing the effects of a type of drug called anthocyanin, or more specifically, cyanidin-3-glucoside (C3G). We expected C3G to affect a dark-adapted cell’s sensitivity, most likely acting as an inverse agonist, based on other experiments done with anthocyanins and on the preliminary screen. However, we did not see any significant change in sensitivity among the varying cells we tried, so we decided to move to a new drug called D-pyroglutamic acid (DPA). The preliminary biochemical screen suggested DPA to be an agonist for opsin. We had to run many experiments in order to determine a pattern of activity, but it appears that DPA bleaches red-sensitive cone rhodopsin and activates green rod free opsin (but not its rhodopsin). However, I would have liked to see our last experiment (adding 9-cis retinal to regenerate the pigment bleached by DPA) run a couple more times, as reproducible results would help to confirm our results.

Hopefully the future study of DPA’s effects on opsin, as well as the study of other such compounds, will reveal any allosteric binding sites present on opsin that could be used to counteract genetic mutations in the phototransduction system. Most of all, my work this summer taught me most of all to think inquisitively and to work patiently; I know I will take these skills with me into all my future scientific endeavors.

Ling (Ivy) Tao

(Dr. Shelley Pressley, Laboratory for Atmospheric Research, Washington State University)

Research Summary: Thanks to the Howard Hughes Medical Institute’s sponsorship of Science Horizon Scholarship, I was able to participate in a summer research program that is otherwise only available for undergraduates with US citizenship or residence. As an international student with external funding, I participated in the Research Experience for Undergraduates Program at Laboratory for Atmospheric Research in Washington State University. This is a program that brings together students from a variety of science and engineering majors to do individual research projects related to atmospheric experiment and simulation for ten weeks.

For me, the experience is especially valuable, because I was considering going into Environmental Engineering with an undergraduate major in Physics, but did not have a clear idea of the field. But the ten-week long intensive research convinced me that it is indeed a great career.

First of all, I had a great time learning about a whole new field and tried to research a specific topic in a short period. My research topic is on the regional variation of air quality as a result of wildfire atmospheric emissions, and how future climate may change the patterns. In order to understand the topic, I needed to know the chemical composition of the pollutants output by wildfires, and how these pollutants transform over time in the atmosphere. I also needed to learn about the ozone cycle, the importance of atmospheric nitrogen compound ratio, and deposition theories of particulate matters. Laboratory for Atmospheric Research did an excellent job in preparing us the basic knowledge in Atmospheric Science, by giving us a series of “crash courses” throughout the research period, concentrating in the first two weeks. Because all the professors are very familiar with their own specialized fields, they gave comprehensive lectures and effective hands-on exercises during these “crash courses”.

Knowing the background materials, I started my project, one that is technically challenging. I had to learn a programming language that is good for statistical analysis and Linux-based operation and coding. I feel that one reason I learned these relatively quickly is that I have an advisor who is a Ph.D. candidate, in addition to two other advisors who are professors. I felt more comfortable asking for help from the Ph.D. student when I encountered minor programming problems. Nevertheless, when it comes to the analysis of the data and the direction to go into for the project, I would discuss the issues in the weekly meeting for four of us, or go to one of the professors. At the end of the research, each of the students was required to produce a poster of the result and present it in the final symposium. This part of the program enhanced my presentation skills greatly, since I had never done an oral presentation for any of my research before. Now I feel confident in making an effective poster and explain it in a few minutes. The only regret I have is that no paper was required at the end of the research, due to the time constraint. But overall, doing this research project enhanced my ability greatly in various different ways.

In addition to the above positive experiences, I had a worthwhile summer living in a house full of science and engineering students. This is much less trivial than it sounds, since we had after-dinner discussions on our own researches and current scientific news, and the atmosphere in the house was great for anyone who is interested in science and engineering as a life-long career. During the program, we were also invited to lunchtime info sessions on graduate studies in different areas, and made a trip to the Pacific Northwest National Laboratory to look at the current researches going on there.

In sum, I came back to my college knowing for sure what I want to do in graduate school and how to edge my way into Environmental Engineering, and more specifically, in Atmospheric Research. The summer proves fruitful for me and I am very grateful for the funding opportunity provided by the HHMI.

Kerstin Baer

(Mentor: Dr. Herman Gluck, Professor of Mathematics, University of Pennsylvania)

Research Summary:  My work this summer focused on finding mathematical ways in which “visually nice” geometric objects are mathematically optimal. Past work concentrated on identifying volume-minimizing cycles in a given homology class of various homogeneous spaces. While this approach was quite fruitful in low dimensions, it led to unexpected results in higher dimensions. For example, the Hopf vector fields are volume-minimizing cycles in the unit tangent bundle of the three-sphere (Herman Gluck, Wolfgang Ziller) but not for higher-dimensional spheres (Sharon Pedersen).

The research group has recently embarked on a new approach. Instead of minimizing volume, they are identifying maps that minimize stretch. The hope is that “stretch”, being an inherently one-dimensional measure, conforms closer to our low-dimensional intuition than a high-dimensional measure such as seven-dimensional hyper-volume. Early results are promising. For example, Herman Gluck, Dennis DeTurck and Peter Storm have shown that the Hopf vector fields, when viewed as a map into the unit tangent bundle, are Lipschitz minimizers in their homotopy class in all dimensions.

This summer I have been working alongside a few graduate students at the University of Pennsylvania. We have been searching for other “nice” examples of Lipschitz-minimizing maps and investigated general properties of the Lipschitz constant of maps between geometric spaces. We have found asymptotic bounds for the Lipschitz constant of degree d maps from an n-sphere to itself, for large values of d. Currently we are investigating properties of the torsion generator of the 7-dimensional homotopy group of the four-sphere, after it was shown that the corresponding Hopf map is the unique Lipschitz-minimizing generator of the free part of this group.

As the project is still in its early stages, the focus is on studying explicit examples to get an idea for how the general theory should go. The hope is that all Riemannian submersions of sufficiently nice manifolds might be Lipschitz minimizers in their homotopy class. I am looking forward to continuing my work with this research group in my senior year and developing my insights into my senior thesis. It has been very exciting to be part of the development of a new theory in its early stages. I also had the opportunity to attend weekly meetings for another project that my mentor has been working on, and I met some of his collaborators in other states. It has been a very rewarding summer.

I am deeply indebted to Herman Gluck and Dennis DeTurck for their guidance, suggestions and patience with my never-ending ignorance. I would also like to thank the Howard Hughes Medical Institute for funding my work and giving me the opportunity to experience life as a mathematician for a summer.

References:

1.NASA. “NASA images of Wildfires”. NASA/MODIS Rapid Response. Access on 30 July 2010.http://www.nasa.gov/vision/earth/lookingatearth/socal_wildfires_oct07.html
2. Skamarock, W.C., J. B. Klemp, J. Dudhia, D. O. Gill, D. M. Barker, W. Wang, J. G. Powers, 2005: A Description of the advanced Research WRF Version 2. NCAR Tech Note, NCAR/TN-468+STR, 88pp.
3. Guenther, A., Karl, T., Harley, P., Wiedinmyer, C., Palmer, P. I., and Geron, C.: Estimates of global terrestrial isoprene emissions using MEGAN (Model of Emissions of Gases and Aerosols from Nature), Atmos. Chem. Phys. Discuss., 6, 10107-173, doi:10.5194/acpd-6-107-2006, 2006
4. US Environmental Protection Agency. “2002 National Emissions Inventory Data and Documentation.” Access on 1 August 2010 http://www.epa.gov/ttn/chief/net/2002inventory.html#documentation
5. DW Byun, JKS Ching,1999:  Science algorithms of the EPA Models-3 community multiscale air quality (CMAQ) modeling system. Rep. EPA/600/R-99.
6. R Development Core Team (2008). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org.
7. Avise, J., Chen, J., Lamb, B., Wiedinmyer, C., Guenther, A., Salathé, E., and Mass, C., Attribution of projected changes in summertime US ozone and PM2.5 concentrations to global changes, Atmos. Chem. Phys. 9, 2009.
8. Chen, J. Avise, J., Lamb, B., Salathé, E., Mass, C., Guenter, A., Wiedinmyer, C., Lamarque J.-F., O’Neill, S., McKenzie, D., and Larkin, N, The effects of global changes upon regional ozone pollution in the United States, Atmos. Chem. Phys. 9, 2009.

 Jenna Pfeiffer

Reflections:

Before the Institute …

When I first inquired about working as an intern with Dr. Grobstein and Wilfred Franklin in the K-12 Pre-College Summer Science Institute, I admit that I hardly knew what that would involve. The only thing that I did know is that my main interest in the summer institute came from the fact that I was interested in the apparent dichotomy between an “English” brain and a “science” brain. I assume my main interest in this was how to bridge the gap between the two and somehow discover ways in which educators can make science less intimidating. Much of this motivation to “debunk”, if you will, the idea of science as being intimidating came not from my own experiences, but rather from the experiences of my sister and many peers. Time and time again I would witness a countless number of my friends and peers proclaim that they never entered Park Science Building at Bryn Mawr because they did not identify as “science” people and that they would never enter Park because all of the classes that were held there were far beyond their interest or even comprehension. 

Beginning Thoughts…

With this being said, I still admit that although I knew one of my interests in working at the institute was what I mentioned above, I was still unsure of what exactly I would be doing in the institute. I had many people ask me what I was doing during the summer, yet after I told them they did not seem to understand. I will admit that I became increasingly frustrated when several of my peers questioned how such an internship was comparable to the science research that they were performing. It appeared as though they were also confused because while they spent ten weeks working in a laboratory, myself, Kate, and Jessica were spending our ten weeks preparing materials that would be discussed with the teachers. Essentially, I guess the most difficult idea for them to grasp was the difference between the two mediums that we were working with. While the majority of the summer science interns were accustomed to working with inanimate objects, chemicals, and data, our laboratory was concerned more with people and current issues in education.

Although I knew that there was quite a difference between our lab and many of the others during the summer, I still did not know exactly how the work that we were doing during the weeks that lead up to the institute would coincide with the actual things that we would be accomplishing in the institute. Furthermore, I was also a bit confused what exactly the internship would entail. Although I knew the general themes that would be covered I could have never anticipated much of the things that would be accomplished in the institute. For a while myself, Jessica, and Kate were also concerned that we did not have enough material to cover the three weeks of the institute. We were incapable of comprehending how far that material that we had would stretch and doubted that it would do so for three weeks! Lastly, one of my “anticipations” for the institute was the concern that the members of the institute would not exactly “gel” very well.

Carrie Schoonover

(Mentors: Dr. Sally Radovick and Dr. Chris Romero, Department of Pediatrics, The Johns Hopkins University School of Medicine)

Research Summary: Pituitary development requires a number of different signaling molecules and transcription factors, which are expressed in a temporal and spatial manner, in order for normal development of pituitary progenitor cells of the specific pituitary cell types to occur. These cell types include the somatotroph, thyrotroph, lactotroph, gonadotroph, and corticotroph. If interrupted by abnormalities, this cascade of events can lead to the failure of specific cell types to develop or affect their ability to correctly produce hormones. There is a population of patients, usually neonates and children, who present with pituitary hormone deficiencies without a specific etiology, also known as combined pituitary hormone deficiency (CPHD). Over the past several decades, there have been an increasing number of reports of patients with CPHD that have documented mutations in these pituitary developmental factors, which has yielded greater insight into the genetic basis for the development of CPHD. This summer I worked in a pediatric endocrinology lab at the Johns Hopkins University School of Medicine. The lab is headed by Dr. Sally Radovick and I worked under the direction of Dr. Chris Romero. The goal of my research was to screen the DNA of patients diagnosed with idiopathic CPHD for mutations in the gene encoding the developmental factors involved in pituitary development.

For the first few weeks I spent time reintroducing myself to the techniques of the polymerase chain reaction (PCR) and gel electrophoresis and learning how to extract genomic DNA from whole blood samples. I also worked with Dr. Romero to further understand the development of the pituitary and the specific genes required for normal development, and I assisted in the compilation and organization of clinical data pertinent to study subjects. Given that this is an ongoing project, the combined efforts of a number of people allowed for the development of a “PCR Panel,” a table that outlines the experimental conditions (temperature and buffer) for each exon of the eight transcription factors of interest (HESX1, LHX4, LHX3, PITX2, PIT1, OTX2, SIX6 and PROP1). The panel is the result of many optimization experiments in which various temperatures, buffers, and primers were used in order to find the combination that gives the best result (i.e. the strongest and cleanest band in the gel). Despite this, I encountered a number of roadblocks in my project, most often when PCR didn’t produce distinct bands or any bands at all. This led to a series of experiments in which I optimized the conditions again. We tried different buffers, temperatures, and eventually created new primers that included a different DNA sequence.

Once I found a systematic method to perform the PCR on several factors, I was able to screen the DNA of multiple patients at one time. As soon as I had distinct samples, I prepared and sent them for sequencing (our lab outsources the sequencing but we read the sequences ourselves). When reading a sequence I looked at the base pairs (which are color coded) and the peaks to determine if there were mutations or deletions. I used a few different programs for reading sequences: NCBI BLAST compares the experimental sequence to the database of known sequences for human DNA and tags any differences. I used a second program called DNADynamo to determine if the base pair changes resulted in a different amino acid. Unfortunately I did not find any mutations or deletions during my research, but my contributions to the project will hopefully simplify the screening process.

Most of my time was spent in the lab, but once a week I shadowed Dr. Romero in the clinic, where I saw patients with a variety of endocrine disorders. Through listening to the patients and talking with Dr. Romero I gained a greater appreciation for the intersection of research and the clinical experience and how advancements in research can affect how patients are treated in the clinic. I was also reminded of the “communication gap” between doctors and patients, something that can complicate the process of finding the right treatment plan. For me, this experience reinforced the necessity of patience in lab research and introduced me to new possibilities for combining my interest in research with my goal of becoming a practicing physician.

Camilla Montonen

(Menotr: Dr. Arkady Yartsev in the Department of Chemical Physics at Lund University, Sweden.

Ultrafast electron injection and recombination in a porphyrin sensitized solar cell

Research Summary:
Introduction: The porphyrin sensitised solar cell (PSSC, for short) has the potential for becoming an important source of alternative energy. The production of electricity in a PSSC is driven by electron transfer reactions. In short, a photon of light excites an electron in the dye molecule, which is subsequently injected into a network of titanium dioxide particles. The electron then diffuses through this network into an external circuit. Meanwhile an iodide/tri-iodide redox couple reduces the oxidized dye. In addition numerous other processes take place, such as electron transfer back from the titanium dioxide network to the dye known as recombination.

Since electron injection and recombination are important parameters, which determine the efficiency of the PSSC, these reactions were studied with transient absorption spectroscopy, a spectroscopic method in which a sample is excited with a laser pulse and then probed with another pulse with varying time delays.

Research questions
The scope of the investigation included three main research questions:
1) How does the presence of the iodide/tri-iodide redox couple affect the kinetics of electron injection and electron recombination in a PSSC?
2) How do the electron injection and recombination kinetics differ in open circuit as opposed to short circuit conditions?
3) How different are the electron injection and recombination kinetics in a plain glass PSSC (usually used in spectroscopic measurements) as opposed to a conductive FTO glass PSSC (FTO glass is used in real life functioning solar cells)?

Results and conclusions
1) The presence of iodide/tri-iodide redox couple slowed down the rate of electron injection as compared with the injection kinetics of a PSSC containing simply acetonitrile as the solvent.  This may be perhaps due to the way iodide/tri-iodide affects the bending of the molecule, thus forcing the porphyrin moiety farther from the surface of the TiO2 and decreasing the rate of electron injection.
2) There was no observed difference in electron injection between open circuit and short circuit conditions.
3) The rate of electron injection was accelerated in a PSSC prepared on conductive FTO glass as opposed to a PSSC prepared on plain glass. The reason for this wasnot determined in the experiments.

Natalie Mackow

(Mentor: Dr. Jake Kushner, The Children’s Hospital of Philadelphia)

Histopathology of CFTR mutant and knockout pig pancreata: a model for CFRD?

Research Summary:  An inhibition of ß-cell function (insulin deficiency) in the pancreas of CF patients often leads to a development of cystic fibrosis related diabetes (CFRD) and this comorbid disease has become increasingly prevalent in CF patients as life expectancy has increased. A very high percentage of patients with CF are homozygous for the ∆F508 mutation of the CFTR gene and a majority of individuals with CFRD are also homozygous for this mutation. An increased mortality rate has been observed in CFRD patients in relation to CF patients, especially in females, marking CFRD as a major clinical problem. However, the mechanism by which CFRD occurs is poorly understood. Additionally, the mouse, the animal model most often used to investigate human diseases, does not develop cystic fibrosis of the pancreas and is thus inappropriate for studying CFRD.

My goals this summer were to (a) determine whether ß-cell proliferation differs in wild type versus CFTR knockout (-/-), and ∆F508/f508 mutant pigs; (b) determine whether ß-cell mass and/or function in the pancreas is affected by CFTR mutations and contributes to the mechanism of CFRD; and (c) further establish the pig as a viable animal model for future use in preclinical testing of CFRD therapies. In other words, we wanted to know whether CFTR is required for normal ß-cell function and, alternatively, whether CFTR is required for ß-cell mass expansion and/or function after birth. These and future studies in the Kushner lab will define changes in pancreatic islets resulting from CFTR mutations and establish parameters for assessing the histopathology of CFRD.

            Embryonic and neonatal pigs with genotypes CFTR +/+, CFTR -/- and CFTR ∆F508/∆F508 were generously provided by members of the University of Iowa. Immunohistochemical staining was performed using guinea pig anti-insulin and mouse anti-ki67 (a marker for cell proliferation) as primary antibodies. Secondary antibodies were cross-absorbed and labeled (Cy3 and Cy5) and DAPI (4’,6 diamino-2-phenylindole) was used for nuclear staining. Images of samples were taken and analyzed using Volocity 4.0 analysis software and a specialized protocol.

I worked on this project last summer for a Gene Therapy undergraduate program at UPenn, and was easily able to re-familiarize myself with techniques. I had already performed a good portion of the immunostaining, making it easier for me to analyze a large amount of slides and samples. Likewise, I was better acquainted with Volocity and re-analyzed data from the previous summer, making sure that all samples were analyzed using the same protocols and restrictions.

We found that ß-cell area (the concentration of ß-cells in a sample) was significantly reduced for CFTR -/- compared with CFTR +/+ (p = 0.0087) but was not significantly reduced for CFTR ∆F508/∆F508 (p=0.101) in embryonic pigs. This suggests that CFTR is involved in maintaining normal insulin levels in the pancreas. However, ß-cell area varies depending on which portion of the pancreas was cut. Our data suggests that there is no significant difference in ß-cell area in affected neonatal pigs (CFTR -/- p=.860, CFTR ∆F508/∆F508 p=0.900), but there was a wide variation in area between individual samples. For example, a majority of CFTR F508/∆F508 had low ß-cell areas and only a few had high ß-cell areas. This discrepancy could be explained if we knew which section of the pancreas was cut. As for proliferation, a paired T-test determined the difference between neonatal CFTR +/+ and CFTR -/- and CFTR ∆F508/∆F508 ß-cell proliferation to be insignificant.

1 CFTR +/+ and 1 CFTR -/- sample were stained for M3A7, a CFTR antibody, to determine the location of this chloride channel in the porcine pancreas. CFTR was observed in the intercalated ducts of the wildtype pancreas and, as expected, an absence of CFTR was observed in the knockout. These ducts were not observed to overlap with islets, suggesting that CFTR is not present within ß-cells.

It may be too early in the pig's development to observe, quantitatively, the difference in ß-cell area or ß-cell proliferation. However, the images taken demonstrate that CFTR -/- and CFTR ∆F508/∆F508 porcine pancreata appear dramatically different from normal CFTR +/+ pancreata. This change in appearance likely would lead to a significant deficit in pancreatic function in pigs. Likewise, the porcine disease seems to be accelerated in comparison to the human disease in that the pigs were born with meconium ileus and radically different pancreata (in appearance), including fatty infiltration and atrophic acini. Overall, the pig may be a very good model for CFRD. It certainly looks like a good model for CF, as knockout and homozygous mutant animals consistently and similarly developed class cystic fibrosis of the pancreas. It will be interesting to examine the development of the disease in older pigs, if possible. CFRD is most common in individuals with CF as they get older (>20 years) and this is likely the same in pigs as well. 

My lab and I are excited to get started on a paper on this topic! We are in the process of analyzing the pancreata of human newborns who died of CF, comparing them to controls, and pairing them with my pig data to see the similarities and differences in the histopathology of CF.

Yuhou Xia

(Mentor: Dr. Daniel Lidar, Center for Quantum Information Science & Technology, University of Southern California)

Research Summary:  This summer, I did research in Center for Quantum Information Science & Technology (CQIST) at University of Southern California.  The project I worked on was in a branch of quantum computing.  A quantum computer is a machine that does computation using quantum mechanical properties of particles such as spin and entanglement.  Due to these properties, a quantum computer with only several qubits (quantum bits) can solve some problems faster than any classical computers.  However, quantum computing is still a new subject and there are a lot of problems that need to be solved.  One major problem in practice is that the quantum bits (qubits) tend to couple with their environment (bath) which results in decoherence that will cause computational errors.  Over the years, various ways of suppressing quantum decoherence have been explored.  The one I worked on was dynamical decoupling in which one applies a sequence of strong pulses to decouple the qubits from the environment.  This method is based on Hahn spin echo.

There are several known pulse sequences in dynamical decoupling.  Uhrig dynamical decoupling (UDD) is the optimal sequence to decouple one qubit subject to pure dephasing or longitudinal relaxation from its environment.  Quadratic dynamical decoupling (QDD) is a near optimal sequence we get by nesting two UDD sequences to decouple one qubit subject to general decoherence.  QDD is a special case of nested Uhrig dynamical decoupling (NUDD) which decouples a multi-qubit system subject to general decoherence from its environment.   It is helpful to know the performance of these sequences.  In 2010, Dr. Uhrig and Dr. Lidar derived a rigorous performance bound for UDD.  My research topic this summer was to derive a rigorous performance bound on QDD and NUDD.  Due to the computational complexity in the NUDD case, we actually took a slightly different approach than that in the QDD case.  But the behaviors of the bounds we got for QDD and NUDD were similar.  Our main results were analytical upper bounds, for QDD and NUDD, on the trace-norm distance between the states of the DD-protected qubit or qubits, and the unperturbed qubit or qubits, given as a function of the total evolution time and the norms of the bath operators. Under the assumptions that the bath operators have finite norms, the upper bound for NUDD showed that the trace-norm distance could be made arbitrarily small as a function of the minimal decoupling order N of the UDD sequences comprising the NUDD sequence. In the QDD case, a tighter bound was obtained by having different decoupling orders for different types of decoherence errors.

I would like to thank Howard Hughes Medical Institute and Bryn Mawr College for their generous support for my research this summer and NSF Quantum Information Center for Quantum Chemistry for giving me the opportunity to participate in the research.  I would also like to thank Dr.Daniel Lidar for being a very helpful and patient mentor.   This has been an invaluable experience for me and it makes me more certain of a career as a scientist.

Anna Jaffe

(Kathryn I. Pollak, Ph.D., Comprehensive Cancer Center, Duke University)

Research Summary: My Science Horizons Internship funded by the Howard Hughes Medical Institute has opened up many opportunities for me.  I was able to be a part of the TeenCHAT (Communicating Health, Analyzing Talk) research team that I was a part of during the summer of 2010, but I also had the opportunity to think more critically about the project and come up with my own questions within the study. 

Sponsored by the National Heart, Lung, and Blood Institute, the TeenCHAT project at Duke University is investigating and attempting to improve how doctors communicate with overweight adolescent patients about weight-related behaviors. During Phase II of the study (the phase we began this summer), half the doctors are given a motivational interviewing intervention. Aside from my individual research, my role within the study was to interview eligible patients before their yearly physical on topics such as drug and alcohol use, sexual activity and condom use, as well as eating and exercise habits. After meeting them at and audio-recording the visit with their physician, I surveyed both patient and doctor about their interactions during the appointment.

Last summer, I became especially interested in how much control adolescent patients felt they had over their lifestyle, as well as their outcome expectations, confidence, and motivation with regard to weight related behaviors (losing weight, improving diet, increasing exercise). After reading many different studies examining either confidence or parental control in relation to adolescent weight, I found that the interaction between the two variables had not been thoroughly investigated. My research question examined a possible association between adolescents’ confidence in their ability to lose weight, increase exercise, and improve diet with their reported balance between levels of parental control over those factors.  I thought that if the confidence, motivation and outcome expectations with regard to weight-related behaviors felt by adolescent patients was correlated with reports of parental control, then perhaps physicians could find ways to counsel adolescent patients on ways to take more control over their weight, diet, and exercise habits.  I also considered other factors with regard to weight-related behaviors, such as age, gender, race, BMI, and adolescents’ wish to lose weight.

One of the most exciting parts of the summer was learning to interpret my results and data.  I haven’t taken statistics, so learning how to look at the different tests and values was fascinating.  I also learned the frustrations of research as well: none of my hypothesized correlations were significant.  While none of the parental control factors was associated with weight-related behaviors, there were some unexpected significant correlations (p≤ 0.05) that appeared in relation to demographics. Some of the weight-related behaviors of motivation/confidence/outcome expectations with regard to diet, exercise and losing weight were significantly correlated to race.  Adolescents who self-reported race as “Black/African-American” were more likely to have high outcome expectations (a 5 as “very much so” as opposed to 4 or below), higher motivation and higher confidence with regard to some of the weight-related behaviors than adolescents who self-reported as “White”. However, this was not a part of original hypothesis, and so we had not controlled for BMI in our analyses; I have plans to investigate this aspect further, although my limited time this summer did not allow for it.

As parental control was not associated with adolescent motivation, outcome expectations and confidence regarding weight-related behaviors, additional research is needed to determine what effect parental control over adolescent’s diet and exercise habits has on their behavior.  This research could help physicians work together with both adolescents and their families to gain a healthy weight. While my initial hypothesis was not correct, the demographic correlations that appeared will also be important to investigate further.  Perhaps BMI was confounding those results, or perhaps there are cultural differences with regard to perceptions of weight that affect these variables. I am currently working with Dr. Pollak and the team to look at some of these aspects.

As I am hoping to attend medical school after Bryn Mawr, working on the TeenCHAT project has been the perfect vehicle for my interests. I have learned of the power of preventive medicine to improve long-term health outcomes; investigating ways to improve and optimize health care delivery is important. As medical science and technology continue to evolve, the need to identify the most effective methods of communication and health care delivery should not be overlooked. Aside from learning the importance of clinical research, being a part of TeenCHAT has also given me the opportunity to recognize the importance of a trustworthy doctor-patient relationship; this will be essential in my future as a physician. I have also become aware of methods such as motivational interviewing that can help doctors communicate with patients about behavioral issues such as weight, diet, exercise, smoking, drinking, and medication adherence. When looking at the data our team has collected thus far, it was fascinating to see differences between how doctors and adolescent patients felt about the same interactions during a physical.

Yolanda Yue Shao

(Dr. Bruce Weir and Dr. Kathleen Ker, Department of Biostatistics at the University of Washington.)

Research Summary

The 10 weeks at the Department of Biostatistics, University of Washington has truly been a fulfilling and memorable experience. Not only did I acquire much knowledge on statistics, genetics and computing, but also experienced what it is like to be a biostatistician and learnt more about what I want to do after college.

I spent the first two-and-a-half weeks taking 5 modules, all taught by professors from the department, at the 16th Summer Institute in Statistical Genetics. The classes provided a good background for my later research, equipping me with a general understanding for human genetics, R programming and the statistical tests that are commonly used.

My research was focused on exploring the association between inbreeding and long runs of homozygosity. Inbreeding is an important concept in genetics because the usual tests that scientists use assume that the observed genotypes come from unrelated subjects in a random mating population.  If there is inbreeding, those tests are not valid. We cannot observe inbreeding directly from the genome of a population, but we can observe homozygosity, and inbreeding increases the probability that offsprings are homozygous. There are many measure of homozygosity, so my goal was to find one that is highly correlated to an individual’s inbreeding coefficient. I experimented with the proportion of homozygosity, the longest run of homozygosity and the maximum LOD score for each individual, and concluded that the LOD score is best “indicator” for an individual’s inbreeding coefficient.

Learning R programming was one of the most challenging parts of my research. I came with no prior experience in programming, but I had to use R for most parts of my research. I learnt some R in the summer institute, but writing codes on my own was very different from reading the codes from others. I spent many nights debugging my program but the hours often went fruitless. But I will never forget the immense joy and satisfaction I had for those moments when I finally did locate the problem and my program started to function.

I was very fortunate to have Professor Bruce Weir as my mentor, whom I worked directly with for most parts of my research. Prof. Weir is internationally famous in this field, and he proved to be one of the most professionally accomplished and dedicated people that I know. He is a very rigorous scholar and gave me guidance and directions throughout my research. On top of that, he is also an extremely patient and helpful mentor. He had many other commitments, but he never failed to find time to meet me to discuss my progress and questions. I benefited so much from him not only in terms of knowledge, but also the altitude towards work and life.

Other than the research itself, I interacted with many phD students on a day-to-day basis and got to know about the life as a biostatistics graduate student. Prof. Weir also connected me with the admission of the graduate school. I also became more informed of the structure and rigor of a phD program and the stress and commitment that I should expect. After this experience, a graduate program in biostatistics is definitely a path I want to consider after Bryn Mawr.

I am deeply indebted to many people and organizations that were instrumental for the completion of this project. Howard Hughes Medical Institute and Bryn Mawr College kindly sponsored the Science Horizon Research Fellowship which funded my research. Other than much scholarly guidance, Professor Bruce Weir also offered a scholarship to attend the 16th Summer Institute in Statistical Genetics. Professor Kathleen Kerr helped to make the initial contact and gave me much support and suggestions before and during the research. Charles Cheung, Jess Shen and Xiuwen Zheng answered my questions in R programming. Without them this project would not have been possible.

Qian Wu

(Mentor: Dr. Daniel Koditschek in the School of Engineering and Applied Science at the University of Pennsylvania.)

Research Summary:  In this summer, I worked with Dr. Daniel Koditschek and his PHD student, Avik De from University of Pennsylvania on point-cloud segmentation methods. Point-cloud segmentation is the process of dividing point clouds into meaningful regions in order to obtain important geometrical information. Persistent homology¹ can be applied to feature detection and shape recognition. This is very promising for sensing system of robots. It is possible to build a family of topological spaces called simplicial complexes from point data using the Vietoris-Rips construction¹. Persistent homology aims at detecting geometrical features, such as holes that persist over a significant parameter range while filtering out short-lived noise that arise from in accuracies in the scanning and merging process².

In the first few weeks, I learnt about basic functions in Matlab and theoretical knowledge of persistent homology with the guidance of Avik. We also had biweekly meetings with Dr. Koditschek to discuss my progress and future direction of my research. In the meantime, I observed other research group’s work in GRASP lab of University of Pennsylvania. It is very beneficial for me to talk to PHD students about their experience and know what the world of robotics is like.

Through numerous tests and discussion, we find that compared to other segmentation methods, persistent homology is able to detect features that persist for a large parameter scale. More importantly, persistent homology does not require models to classify objects. This is especially important for robots in unknown environments. Toolbox “JPlex” is capable of handling a large number of data points by selecting a few landmark points and still producing relatively accurate results. Future work can be done to include robot motion as a parameter in homology group calculation as we want to detect persistent features as robot moves around in space. An algorithm for the robot to interpret persistent intervals needs to be designed as well. In addition, we can further improve computational efficiency and reduce calculation time for a large number of points.

I thank Howard Hughes Medical Institute for its sponsorship of Science Horizon Scholarship, which provides me with wonderful research opportunity. I am also deeply indebted for the guidance and help of Dr. Koditschek and Avik De.

Reference:

1 R Ghrist. Barcodes: The persistent topology of data. Bull.Amer. Math. Soc., October 2007

2  Guskov, I., and Wood, Z. 2001. Topological noise removal.In Graphics Interface 2001, 19-26

Aijingwen Li

(Mentor: Dr. Ya-Ming Hou, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA)

Genetic testing is being increasingly used in modern society. DNA-based testing allows the genetic diagnosis of vulnerabilities to inherited diseases and is employed to determine identity and parentage.  In the future genetic testing will probably make personalized medicine a reality by predicting which of several drugs are most appropriate for a given patient. The most common method used to detect a genetic polymorphism for clinical testing and forensics is to PCR amplify the DNA of interest and sequence it in a core lab. However, it usually takes more than 24 hours to get the results. It would be much more productive and efficient if doctors could conduct genetic testing in the office or if police could analyze blood or other samples at the crime scene. Hence, my summer project was focused on designing a faster way for genetic testing based on SNP genotyping by direct hybridization.

A single nucleotide polymorphism is a base pair substitution at a particular locus within a DNA sequence. SNPs are the simplest and most abundant type of genetic variation in human beings. Upon choosing a pool of suitable SNPs with known genotypes for qualification, we conducted SNP discrimination assays using fluorescently labeled stem-loop probes. Stem-loop probes are more specific than linear probes due to competition between intramolecular pairing of bases in the stem of the probe and intermolecular pairing between probe and target. Each SNP was addressed using a pair of probes, reflecting the two possible sequences bearing the SNP in question. By analyzing the ratio of signal strength of the perfect-matched hybrid to the signal strength of the mismatched hybrid, we managed to select 26 potential SNPs out of a group of 39 SNPs. We then proceeded to test the resolution power of paired FAM/Cy5 or FAM/Q670 labeled probes for each potential SNP. Most of the probes worked well with their corresponding SNP.  Finally, we selected 20 SNPs in which the minimum fold change in Cy5/FAM or FAM/Q670 ratios between a heterozygous standard and a homozygous standard was between 3.5 and 10.  SNPs 7, 9, 14, 15, 22, 24, 25, 26, 33, 34, 38, 40, 42, 43, 49, 50, 51, 59, 61, and 67 met this criterion.

The main focus of this project was to simplify the process of human genotyping. Hence, it was important to make sure that the 20 chosen SNPs and their respective probes worked well not only with synthetic single-stranded DNAs, but also with PCR amplified DNA prepared from human genomic DNA samples. We obtained human CEPH (Centre du Etude Polymorphisme Humain) DNA samples from a commercial source and tested the ability of our qualified probes to correctly genotype the respective SNPs. By comparing the relative ratios of FAM to Cy5 fluorescence obtained with homozygous and heterozygous standards to the ratio obtained with each CEPH DNA sample, we were able to genotype the status of each SNP. 

In conclusion, we successfully qualified 20 SNPs for which the corresponding probe pairs gave good resolution power. As this research is part of an ongoing project, we still need to verify the accuracy of the CEPH DNA genotyping results by comparing them with the results obtained using the SnaPshot assay. Longer term the goal of this project is to automate the hybridization-based typing reaction in the context of a small portable instrument that can complete a genotyping reaction in under an hour. 

I really enjoyed my research experience at Thomas Jefferson University. I am glad that I was able to apply what I learned from biology lessons into helping develop a new biomedical advance. Besides acquiring all the important laboratory techniques, I also learned to have more patience, perseverance and logical thinking while conducting research. In summary, the Science Horizon Fellowship gave me the unique opportunity to explore my interest in science.