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2009 Science Horizons Projects
(Mentor: Dr. Victor Donnay, Bryn Mawr College)
Research Project: Energy sustainability is an important issue in our world today. As the energy needs of the world is increasing, more and more people are trying to reduce their environmental footprints by trying to become sustainable in terms of energy usage. One of the prominent ways of resorting to sustainable energy is by using the most powerful energy sources of all—solar energy. One of the research projects that I focused on this summer was related to solar energy and solar panels.
The opportunity cost of switching to solar energy is different for different people. It mostly depends on where we are located and what our needs are. Most people are likely to switch to solar energy due to environmental concerns. However, there are various factors that affect the payback of switching to solar energy.
There are many things one needs to be mindful of when deciding to install solar panels. The placement (solar array must be placed at an angle that will best capture the most direct sunlight), the sunlight intensity (which is highly affected by the weather), the latitude (how close the place is from the equator), technology (how efficient the solar panel is) and temperature are some very important factors to take into consideration.
Two things I wanted to look at after taking these factors into consideration were energy payback and financial payback. Energy payback is simply the time a solar panel, for instance a Photovoltaic system (PV system), has to operate to recover the energy into making the system. Financial payback, on the other had is the time a PV system has to operate to recover the money that was invested in installing the system.
When I researched the energy payback for different sizes and brands of PV systems, the payback generally ranges from 1 to 4 years. To calculate the financial payback, however, I studied one of the buildings on Bryn Mawr College campus. This can be demonstrated through this simple model I made:
Monthly bill:
Let the monthly bill be $160
- How many kwh do you use per month?
3000kwh (Most home owners use 600-1200 kwh)
- What is the monthly output of the proposed PV system?
Lets assume we are putting 15 kw PV system (15000 watt)
Assuming 7 hours of sunlight,
Monthly output= 15* 7 (Hours of sunlight) * 30 (Number of days)
=3150 kwh per month
- Adjusting for real solar conditions ( Since, solar panels do not perform to their optimum capacity)
Assuming adjustment down to 20%: 3150* 0.8 = 2520
- Divide adjusted output hours by actual monthly average:
2520/ 3000 = 0.84 -> 15 KW panel will cover 84% of the requirements
Savings per month = 0.84* 160
=134.4 per month
- Next divide the initial investment cost by the amount you save in a year.
If the solar panels cost $50,000 to install, assuming the solar panel fully powers the building:
Financial payback = $50,000/ (134.4*12) = 31 years.
Conclusions and Notes:
Through simple modeling and comparisons we found out that solar panels are not economically the best way to reduce Bryn Mawr College’s environmental footprint. However, we will be installing a solar array to power one of our less frequently used buildings for educational purposes.
(Mentor: Dr. Victor Donnay, Bryn Mawr College)
Research Project: We all use energy every day, but we don't necessarily understand what that means. With all of the different measures and units, it is difficult know how much energy we are using and what effect it is having on the world. Additionally, with all of these new "energy saving" gadgets, how do we know when we are actually making a difference?
Math, it turns out, is an excellent tool to evaluate how green your gadgets are. I wrote a unit for a math class that focuses on the question: "Am I lighting my home in the best possible way?". Students are invited to interpret "best possible way" however they choose, as long as they provide evidence to back up their decision.
First, in order to provide an interesting starting point to talking about lightbulbs, I compiled a list of articles in recent news that make lightbulbs more relevant to modern issues. The articles cover the Lightbulb Efficiency Law, the Award-winning LED bulb, and Water-powered lightbulbs. Additionally, there is a TED video that classes can use for discussion that addresses the difficulties of designing energy-efficient technologies for the third world.
Students should not just be able to look up the answer to their question online. Instead, they should prove their answer to themselves through a practical experiment. The teacher should the class into three groups, and each group gets a set of equivalent-brightness lightbulbs. The class’s task is to determine which lightbulb would be the best choice using a wattmeter, laser thermometer, and light meter.
The students might come up with additional ways to measure qualities of their lightbulbs. For example, I can imagine students taking pictures of themselves under each light with their phones in order to tell which one looks better with their completions. As long as they are scientific and methodical in their measurements, this would be a great addition to their data set.
Once everyone has their data, the class should be given two more pieces of information that could be crucial to their decision. The first is the price of each bulb, and the second is how many hours the bulb should last (this should be written on the package).
At this point, the class should have enough data to create a math model. This model can vary from very simple to quite complex, allowing a natural way to incorporate differentiation into the lesson. Analysis of the model can involve mathematical skills like graphing, linear combination, related rates, proportions, unit conversions, and more. At the end of the project, students should have a clear idea of which lightbulbs would be best in which situations, and why. This lesson can make a difference by making math more relevant, and also by giving students experience in using math to make sound decisions.
(Mentor: Dr. Usheva-Simidjiyska, Beth Israel Deaconess Medical Center)
(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.
(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.
(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.
(Mentor: Dr. Georege Amato; American Museum of Natural History, New York)
(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 /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.
(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 (/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 /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.
(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.
(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.
(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.
(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.
(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.
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.
(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.
(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.
(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.
(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.
(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.
In addition to participating on the research project, having a Duke ID afforded me the opportunity to attend Grand Rounds bi-weekly at the Duke University School of Medicine. The lecture topics ranged from Global Health initiatives at Duke University to prolonged Q-T intervals as a factor contributing to possible Torsade’s as well as ethical concerns in the primary care field and 21st Century environmental and occupational hazards/causes of lung disease. Working in my position also afforded me the opportunity to experience the many different pediatric and family medicine clinics around the area, as well as to meet both doctors and patients from each of these diverse locations. The support of Bryn Mawr College and the Howard Hughes Medical Institute allowed me to learn so much about research in the field of clinical medicine; my summer has inspired me to continue this kind of work in my future as a physician.
(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.
(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
(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.
(Mentor: Dr. Ryan F. Hechinger, Marine Science Institute and the Department of Ecology, Evolution & Marine Biology University of California Santa Barbara)
Mapping the Distribution and Abundance of the California Horn Snail (Cerithidea californica) in a Southern California Estuary
Thanks to the Howard Hughes Medical Institute, this summer I had the opportunity to work in the ecological parasitology lab at the University of California Santa Barbara (UCSB) under the direction of my mentor, Dr. Ryan Hechinger. The main focus of study for the lab is to understand the role of parasitism in ecosystems, and to examine the benefits of using parasites as model study systems for ecological and evolutionary theory. The marine gastropod mollusk, Cerithidea californica, commonly known as the California horn snail, is primarily researched at UCSB because it is a very common species, and sole first intermediate host for over 20 species of important trematode parasites. These parasites have complex life cycles where they infect numerous other species in the estuaries, including birds. The horn snails live in many estuaries along the range of the California coast and my research was based in the Carpinteria Salt-Marsh, home to millions of these snails. My project was to create a map of the distribution and abundance (density) of the California horn snail within the channels in the salt-marsh and to better understand the habitat areas and special regions for the snails.
During my first few weeks at UCSB, I read many scientific primary literature articles about the horn snail in order to familiarize myself with the snail, and discussed any questions or thoughts about the papers with Ryan. I had the opportunity to participate in many snail dissections and was educated on the different parasites infecting them. I learned about the different techniques used to extract the parasites from the snail host including dissecting and shedding – a method where a snail is placed in water and then heated to a comfortable temperature coaxing the parasites to leave the host and enter the water. Later, I had the chance to shed and dissect a few snails on my own, where I learned how to identify parasites and gain first-hand knowledge the anatomy of the snail. I scribed for those doing the dissections multiple times and helped crack open the snail shells to prepare for processing. Throughout the first three weeks in the lab, I was trained in appropriate laboratory techniques and all this combined knowledge became valuable when I began my horn snail mapping project.
In the field, the original goal was to create a density map of all channels and open mud areas known as pans. It quickly became apparent that we would not be able to complete this task; before I left Santa Barbara, so the project was simplified to mapping only the channels which are one of the primary habitats for snails. With fine guidelines, and size limits for what “qualified” as a channel, we chose our first point to be at the beginning of every channel and worked upstream. We divided the channel into left and right sides, marked the point on a GPS unit and chose a transect width large enough to capture 25-30 snails across the width of the channel. The depth, horizontal and surface measurements of each transect were recorded for both left and right sides, and on every fifth transect the snails collected were measured to determine the size frequency distribution. We also recorded the percent snail habitat at each site which was identified by what proportion of the channel transect where the snails resided compared to the entire transect size. This piece of data established the ecological density during data analysis. After everything was recorded, we walked 10 meters and repeated the process. In all we sampled approximately 1,300 channel sites.
After collecting the data, I then returned to the lab to finalize data entry and do double-checking. During my time in the field, multiple laboratory undergraduate students assisted us by entering the information we collected from the estuary the day before, which was very helpful, since we had over 2,600 rows of data entered in Excel. My job then was to double check the information that had been input, and if there were any mistakes or discrepancies I marked it on the original field sheet with red. This double checking method allowed us to first off, detect and correct errors, in addition to evaluating the types of errors that are occurring. Even with the assistance of various people, the double checking took a few days, but as soon as I was finished I met with Ryan to analyze the data.
Ryan and I manipulated, plotted, and analyzed the data in the statistical platform, JMP vers. 10. First we overlaid every GPS point onto a Google Earth map so we could see where all the sites were and to ensure there were not any stray points, which there turned out to be a few. We then calculated the count and biomass densities for the sites, plotted them against the ecological density in an X to Y fit graph, and incorporated the line of fit. There was a positive correlation for both graphs made. We also constructed a contour map that displayed a color intensity range in relation to the channel snail density. The deeper shade of red the channel was, the higher the snail density and the deeper shade of blue, the lower the density. With this graph, we found that there were low density areas of snails along the channels closest to the ocean and high density areas in the channels further away, consistent with my expectations from reading the literature. It seems as though that when the proportion of the snail habitat increased across channels, the more snails were living there and more were located in each transect. These high density areas seem to be better living conditions for the snails, although intraspecific competition may be more intense. With these graphs, we concluded so far that as the snail habitat increased, there were a higher number of snails expected to be living in that channel and there were more snails per M2. Snails appeared to do better (that is, have higher fine-scale densities) at sites where they could use a greater proportion of the available habitat. The channel with the higher percent snail habitat is likely to be preferred by the snail and when the snails are restricted to a smaller part of the channel, they are doing less well when they can occupy the entire habitat. The snails could do just as well in the channels with less snail habitat as those in higher percent snail habitat areas, as long as the snails are taking advantage of their entire available habitat.
The research ended here for me but not for Ryan and the two laboratory technicians. A grid type mapping protocol has been designed to determine the density for the rest of the estuary (the pans and vegetated marsh) and they are going to be working on it in the following weeks. After this, the mapping for the entire estuary, channels and pans, will be complete. Making this map will be important for future direction with the laboratory at UCSB. The combined work will provide data for numerous analyses, including more in depth analysis of how spatial location, channel morphology, plant cover and elevation affect snail densities. Further, this mapping will provide a foundation for additional studies examining the role of the snails and their parasites in the entire system, and how that role varies in space. I had a wonderful experience during what I called “The Snail Trail” project, and am very thankful for everyone who made this possible for me.
(Mentor: Dr. Deborah Kim, Department of Psychiatry, Hospital of the University of Pennsylvania)
Exploring the Impact of Maternal Stress on Placental Gene Expression
This past summer, I worked with Dr. Deborah Kim, a psychiatrist and clinical researcher at the University of Pennsylvania School of Medicine specializing in the treatment of pregnant women with antepartum and postpartum depression. I began working with her in the summer of 2011 and became particularly interested and involved in a longitudinal cohort study investigating the impact of antenatal stress and adverse childhood events (ACEs) experienced by the mother on the development of the fetus/infant’s response to stress. Ultimately, this study seeks to examine maternal adverse childhood events and prenatal stress as potential risk factors that may predispose offspring for the development of neuropsychological diseases. Both animal models and human studies have provided evidence that such factors may contribute to abnormal development of the offspring’s stress response.
During that summer, Dr. Kim suggested I read and present a paper that examined the effects of stress and psychotropic medication during pregnancy on placental gene expression. In this paper the effects of stress, not medication, seemed to alter gene expression in the placenta, particularly those involved in the transmission of stress hormones (glucocorticoids) to the fetus. I began to learn more about the placenta, the key barrier that controls what the fetus is exposed to (nutrients, oxygen, stress hormones, antibodies). I learned that a particular enzyme 11β-Hydroxysteroid dehydrogenase (11β-HSD2), which converts cortisol to its inert metabolite cortisone, serves to protect the fetus from excessive amounts of cortisol. It is possible that excessive exposure to cortisol during development may disrupt proper development of the offspring stress response. We began to think of this in the context of our study and realized that incorporating a placental analysis, that examined differential expression of the gene for 11B-HSD2 in our subjects, would serve to examine a possible mechanism by which maternal stress may be transmitted to the fetus.
I spent this summer preparing to carry out this aspect of the study. Two days a week, I worked with a Post-Doc in a biology lab at the University of Pennsylvania School of Veterinary Medicine learning how to analyze genes in the placenta using real-time polymerase chain reaction (RT-PCR) and western blot. Learning these techniques was outside of my comfort zone, as I had never worked in a wet lab before and none of my college course work had ever even covered such processes. In addition, I soon learned that the underlying properties that give the procedures success rely on an understanding of biochemistry. This probably explains why I found the work to be extremely challenging at first and failed to properly complete the procedures several times. Each time I failed, we would try and figure out where the procedure may have gone wrong. This trial and error approach, which I now know to be a routine part of biology of lab research, was something I had never envisioned as part of the process. In order to properly carry out a procedure, not only must one be precise in following the directions, one must also have the correct probes and the correct reagents at the proper concentrations. I found this process to be frustrating, but I eventually was able to successfully complete the protocols. I still do not feel as though I completely mastered the techniques and will definitely still continued practice before I begin processing the placental samples in the actual study.
In contrast to the somewhat secluded setting of the biology lab, I spent the other three days at the Penn Center for Women’s Behavioral Wellness, the Center where Dr. Kim works. There are several human subject based research projects being conducted at this center, which gave me the ability to see the drastically different process that comprises that type of research. Unlike biology lab research, subject recruitment and retention are issues that complicate and prolong the process. These particular issues prevented us from having human placentas to analyze this summer.
While I was at the Center, I conducted a literature search to acquaint myself with the current research on the impact of maternal stress on offspring development, the effects of excessive glucocorticoid exposure on the developing fetus, and mechanisms of fetal programming as it relates to placental gene expression. I created a powerpoint presentation that I presented to the other interns at the research center about my understanding of the current research and my plan to analyze the placentas. This fall, I will be conducting a broader literature search on the topic and will be writing a review for publication under the guidance of Dr. Kim. We expect to have placentas ready for analysis in the spring of 2013.
I also helped Dr. Kim with her novel study looking at transcranial magnetic stimulation (TMS) as a non-pharmacologic treatment for pregnant women with antepartum depression. The subjects in this study came in everyday for 20 days to receive a 15-minute treatment (active or placebo) session. Dr. Kim taught me how to administer TMS and allowed me to treat the women on the days that I was in her office. The women seeking this treatment were severely depressed and upon talking to and observing these women, I realized how debilitating depression could be. Being able to form relationships with them and assess their progress helped to affirm my aspirations for going into medicine.
I found both my experience in the biology lab and in Dr. Kim’s office to be highly educational, in both an academic and personal sense. I learned a lot about the neurobiological basis of the stress response, maternal stress fetal programming, genetics and how all these components are connected. In addition, I was able to see the clear distinctions between human subject based research and basic scientific research. While problems arose with each protocol, different skill sets (genetic analysis requiring a knowledge of biochemistry and subject recruiting/retention requiring a personable nature and a knowledge of human behavior) were needed to troubleshoot each one. This allowed me to appreciate the drastic differences in each type of research.
My experience this summer reinforced my interest and commitment to pursuing clinical research and care. I am more confident than ever that I am traveling the right path. I sincerely thank the Howard Hughes Medical Institute for the funding of this great opportunity and experience. In addition, I wish to thank Christopher Howerton, PhD, who spent countless hours patiently teaching me new and challenging techniques and helping me to understand genetics. Finally, I am truly grateful to my incredibly dedicated mentor, Deborah Kim, M.D., who has been a wonderful role model and teacher through most of my college career. I am lucky to have found a mentor who is so invested in the development of young scientists.
(Mentor:Dr. Andrea Sequeira, Biological Sciences, Wellesley College)
Dynamic Populations: Genetic Signals of Changes in Population Structure in Galapaganus Weevils in Galápagos, Ecuador
Looking at the genetic structure of endemic Galapaganus weevil species on the islands of Isabela and Santa Cruz in Galápagos, Ecuador can provide insight into the present and past conditions of these populations. Single island endemics, such as many of the Galapaganus species under study, are particularly susceptible to environmental change because they cannot increase their population size or gene pool through migration from other islands. Throughout this summer, I worked on two projects in which we collected data for short repeating DNA segments, known as microsatellites. These sections of DNA, located in non-coding regions of the genome, are not subject to selection and are excellent tools for reconstructing the history of populations. Within the past century invasive mammals have been introduced to the Galápagos Islands, including Isabela, which have caused erosion and disrupted the native biodiversity. We were interested in determining whether the genetic signals for habitat fragmentation can be detected in the weevil populations that feed on the plant species destroyed by these mammals. To achieve this we compared the genetic structures of G. conwayensis populations from Northern Isabela and G conwayensis populations from Santa Cruz, an island where habitat fragmentation is assumed to have not occurred. In an area where habitat fragmentation has not occurred, it is expected that populations that are closer together will be more genetically similar, a pattern known as isolation by distance. As predicted, we did not find an isolation by distance pattern among the Northern Isabela populations, suggesting that this genetic signal of habitat fragmentation is detectable in the plant-dependent weevil populations. The second component of my research focused on trying to determine whether populations of the long established endemic, G. williamsi, from Southern Isabela are demographically stable. Computer generated estimates of current and ancestral population size show that a population reduction has occurred. Additionally, comparison of the mean number of alleles and expected heterozygosity of G. williamsi populations with G. conwayensis populations in Northern Isabela indicates that there is no significant difference in the mean number of alleles of these populations. However, Southern Isabela populations have a significantly higher expected heterozygosity, an indicator of higher genetic variation. Since a decrease in population size generally corresponds with a loss of genetic diversity within the population, these results suggest that the genetic potential of G. williamsi populations on Southern Isabela is resilient to the effects of a major change in population size and any environmental and geologic events that may have caused this change.
(Mentor:Dr. Tilo Grosser, Department of Pharmacology, University of Pennsylvania )
Interactions between dietary nutrition and aspirin-‐mediated platelet COX-‐1 acetylation
Low-dose aspirin is one of the most widely used cardio protective drugs. Aspirin inhibits platelet enzyme cyclooxygenase-1 (COX-1) by acetylation of a serine residue in its substrate binding channel to reduce platelet aggregation [1]. A phenomenon of “aspirin resistance” has been proposed, because some patients on aspirin may still have heart attacks, or their platelets may not be fully inhibited. Thus, patients with obesity or metabolic syndrome may have less-than-expected response to low-dose aspirin [2].
The biochemical function of COX-1 is to metabolize unsaturated free fatty acids. Dietary fatty acids which are not the primary substrate of COX-1, might interfere with aspirin’s ability to acetylate the enzyme. These might include (i) palmitic acid, a saturated fatty acid that is very commonly found in plants and animals; (ii) the Omega-3 polyunsaturated essential fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA); and the monounsaturated omega-9 fatty acid oleic acid.
Drs. Li and Grosser developed a novel targeted proteomics assay for direct measurement of platelet COX-1 acetylation by aspirin [3].
The goal of my independent project was to (using the assay developed by Dr. Li and Dr. Grosser) assess whether dietary nutrition including glucose and free fatty acids, some of which usually have elevated levels in diabetes patients, reduces the ability of aspirin to acetylate platelet COX-1 in vitro. MR/MS mass spectrometry was used to measure COX-1 acetylation in human platelets and LC-MS/MS was used to measure thromboxane B2 (TXB2) levels in human platelet-rich plasma (PRP). In addition to my independent project, I also assisted my mentor, Dr. Xuanwen Li with his proof-of-concept clinical study examining NSAID-Aspirin interactions in vivo and in vitro. Non-steroidal-anti-inflammatory drugs (NSAIDs) temporarily block the COX-1 acetylation site. Consequently, many patients who take traditional NSAIDs in conjunction with aspirin exhibit aspirin resistance.
Methods and Materials
Thirty milliliters of human blood were obtained and aliquoted into six 5 mL aliquots. Platelet-riched plasma (PRP) was then isolated by centrifugation at 180 g at 21 0C. The PRP was divided into 300 μL aliquots and then incubated for 45 minutes in a 37 0C water bath with varying concentrations of free fatty acid. Palmitic acid, DHA, EPA, and oleic acid (OA) were the four nonsubstrate fatty acids used, and arachidonic acid (AA, a substrate of COX-1) was used as well. The fatty acids were added to achieve final concentrations of 1 mM, 100 μM and 10 μM. After 45 minutes, all samples except for the negative control (N) were treated with 50 μM aspirin, and then incubated at 37 0C for 1 hour. The platelets were then stimulated with AA (10 μM) for 10 minutes and the samples centrifuged at 2000g for 10 minutes. The supernatant was removed and frozen for thromboxane (TxB2) measurement. To wash the platelets, 300 μl of HEPES 6.8 buffer was added to each sample before centrifuging at 5000 g for 5 minutes. The supernatant was removed and the platelets were resuspended in 40 μL of RIPA buffer for lysis.
The lysed platelets samples were loaded onto a NuPAGE® Tris-Acetate Gel to isolate the COX-1 protein by gel electrophoresis. After staining overnight, proteins in between the 85 and 60 kDa markers were cut from the gel, destained with acetonitrile, and then digested with Trypsin and Glu-C enzymes in preparation for the mass spectrometer. Multiple reaction monitoring mass spectrometry (LC-MRM/MS) was used to detect COX-1 acetylation because it allows for high selectivity and specificity in targeting peptides. Trypsin cleaves the target peptide at the C terminal lysine residue and Glu-C cleaves the peptide at the N-terminal glutamic acid residue. The mass spectrometer targets this peptide because if COX-1 acetylation occurs, the acetyl group will be bound to the serine residue. The difference in mass between acetylated peptides and normal peptides will be detected by the mass spectrometer and allows us to calculate the percentage of COX-1 that was acetylated.
Solid-phase extraction (SPE) with Strata-X Polymeric Reversed Phase cartridges was used to purify the supernatant for thromboxane measurements. LC-MS/MS was used to measure the thromboxane levels.
Results and Conclusions
While the effect of dietary nutrition on human platelet COX-1 acetylation by aspirin needs to be addressed further in vivo, it can be concluded that glucose did not interact with aspirin’s effect on COX-1 enzyme activity and COX-1 acetylation in vitro and that the free fatty acids DHA and EPA dose-dependently interacted with aspirin on COX-1 enzyme activity and COX-1 acetylation in vitro. In addition, mass spectrometric quantitation of serine-529 acetylation is a robust assay for aspirin’s action, which is consistent with platelet COX-1 function assay (TXB2 production).
Works Cited
[1]. Grosser, T., Fries, S., and FitzGerald, G. A., Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 116 (1), 4 (2006).
[2]. Santilli F, Vazzana N, Liani R, Guagnano MT, Davì G., Platelet activation in obesity and metabolic syndrome.Obes Rev13(1):27-42(2012).
[3]. Li X, Fries S, Ricciotti E, Lawson JA, Blair AI, FitzGerald GA, Grosser T. Assessment of The Pharmacological Response to Aspirin by Quantitation of Platelet Cyclooxygenase Acetylation. Circulation 122:A16834 (2010).
(Mentor: Dr. Anna Mapp, Professor of Chemistry, Director in the Program in Chemical Biology, University of Michiga)
Usage of Site-Directed Mutagenesis to Test the Binding Affinity of KIX domain
Understanding the KIX protein-binding domain of the CREB-binding protein (CBP) gives insight into the structure and mechanism of the co-activator CRP and in relation, transcriptional regulation. CBP is the enzymatic domain responsible for histone and transcription factor acetylation. A falter in the regulation of co-activators has been linked to various cancers and genetic disorders. Using site directed mutagenesis; we have created single site mutants of KIX as well as KIX with two mutated sites by transforming the site’s coding for amine acid to a cysteine. Fluorescence polarization is used to identify the anisotropy of KIX binding to the mixed lineage leukemia (MLL) protein and phosphorylated kinase-inducible-domain (pKID), two proteins that bind to KIX in nature. The KIX mutants were also altered by binding small molecules like (1-10) through disulfide trapping to interrogate the binding orientation of the pocket of the mutants structurally and functionally.
With this biochemical information and crystal structures, there is more insight into the mechanism of the co-activators and possible drug discovery.
The process for this experiment is given below.
The plasmid was obtained by running PCR and transformed in DH5α competent Escherichia coli cells. Then the protein was expressed in Rosetta pLysS Competent Cells and purified using Ni-NTA affinity and Ion Exchange FPLC. Then it was buffer exchanged using pD10 size-exclusion column. We confirmed our product by running a SDS-Page gel to show bands near the 14 kDa Lysozyme ladder band. The KIX protein is at the 12 kDA band unless a dimer is formed. For the double mutants, we add DTT in the purification process in order to prevent the formation of dimers, which the percentage increases with the double mutants. This is expected given the increase in disulfide bonds. The single mutant weighed 11897 kDA. When possible, we also used QTOF.
To test the binding affinity of the KIX mutants, we ran binding Fluorescence Polarization corning assays with MLL as well as pKID. By analyzing the fluorescence anisotropy, the dissociation constant may be obtained. If there was a high enough binding, then we will tether on small molecules such as (1-10) and (1-10Cl). The protein with the small molecule was substantiated with QTOF (MS/MS) and then buffer exchanged using NP-40 size-exclusion column.
The results:
With the anisotropy data, we have found evidence the KIX 606 mutant does not bind well at the MLL site, which through cooperative binding affects the binding on the pKID site. Binding the (1-10) molecule also inhibits binding to the extent that on the single mutants, no binding happens.
KIX 664+606 did not bind well as both sides were mutated.
|
KIX |
Kd Value for MLL (μM) |
Kd Value for pKID (μM) |
|
KIX (Wild Type) |
0.63±0.05 |
1.6±0.17 |
|
KIX 627C |
0.11±0.02 |
1.0±0.097 |
|
KIX 627 (1-10) |
1.3±0.22 |
2.1±0.404 |
|
KIX 627 (1-10-Cl) |
1.6±0.22 |
3.0±0.40 |
|
KIX 664 |
0.085±0.0086 |
1.0±0.086 |
|
KIX 664 (1-10) |
12.9±2.29 |
1.4±0.20 |
|
KIX 664 (1-10-Cl3) |
> 20 |
2.3±0.32 |
|
KIX 606C |
> 20 |
17.8±9.47 |
|
KIX 624+627 |
> 20 |
3.8±0.50 |
(Mentor: Dr. David Yousem, The Russell H. Morgan Department of Radiology and Radiologic Sciences, Division of Neuroradiology, Johns Hopkins Medical Institution, Baltimore, MD)
Distinguishing Hemorrhagic and High Protein Containing Lesions in the Brain using Chemical Exchange Saturation Transfer (CEST) Imaging
Research Summary: My summer was spent delving into the world of radiology in new and fascinating ways. I was fortunate enough to have the Director of Neuroradiology at Johns Hopkins and one of the foremost neuroradiologists in the world serve as my mentor. Dr. Yousem offered me the opportunity to work on a project which uses a type of chemical exchange saturation transfer-based MRI technique called Amide Proton Transfer (APT). This technique was recently developed and is being pioneered by the Radiology department at Johns Hopkins.
The purpose of my project was to determine if CEST imaging could be useful in determining the content of cystic craniopharyngiomas. The adamantinomatous form of these neoplasms pose a problem for neurosurgeons because the hemorrhagic and high proteinaceous portions of these cysts look the same on the standard T1-weighted and T2-weighted images. The APT imaging technique, which detects the selective saturation of the magnetization of amide protons through chemical exchange with bulk water protons, has been used to distinguish between tumor and edema in the human brain at 3T. We hoped that our results would show that CEST could provide helpful complimentary imaging pre-op, thereby helping neurosurgeons in choosing a surgical approach (transcranial vs. endonasal).
I began my summer by familiarizing myself with all the relevant literature I could find. Dr. Yousem introduced me to researchers at the Cancer Research Building, the Kennedy Krieger Institute, and the Department of Radiology who could help me. I spent the next ten weeks bouncing between those locations: creating samples of varying concentrations in a lab in the Cancer Research Building, running our samples in an extremely powerful MR scanner (Bruker 500 MHz) in the Kennedy Krieger Institute, and working with our results and the literature in the Department of Radiology. I was fortunate enough to work with some of the brightest minds I have ever encountered, all of whom took the time to ensure I understood what we were doing and why. The final weeks of my project had me communicating with one of the top pediatric neurosurgeons in the world, Dr. Jallo. He was kind enough to jump on board our project and provided us with specimens he collected during his surgeries.
The outcome of our project was a general success. Our in vitro trials showed that the APT imaging technique is able to differentiate between blood and protein in the brain. I look forward to hearing about the future success with this imaging technique once my co-researchers are able to scan patients with craniopharyngiomas. It was so thrilling and rewarding to work on a project that could directly affect the lives of the pediatric patients who suffer from this difficult-to-operate-on neoplasm.
Other highlights from my summer include the lectures I was able to attend and benefit from greatly, such as “Mapping Magnet Susceptibility with MRI in the Brain and Spinal Cord” and “Dynamics of Language Recovery After Stroke”. Additionally, one of the most exciting experiences of my life was the morning I spent in the operating room observing a rib resection followed by a valve replacement. The research and learning experiences of my ten weeks at Johns Hopkins made my summer one I will never forget; I am eternally grateful to the Howard Hughes Medical Institute and the Science Horizons Fellowship for making it all possible.
(Mentor: Dr. Bruce Weir, Department of Biostatistics, University of Washington, F-600 Health Sciences Building)Autosomal, Y chromosomal and Mitochondrial SNPS Independency and Match Probability in Forensic ScienceThis summer was a memorable and enriching experience for me. I was fortunate to have the opportunity working with Dr. Weir on a project in forensic science. Before the research, I didn’t quite have an idea of what forensic science was and how it is related to genetics. Through the research however, not only did I develop profound skills in R programming and understanding of the applications of genetic in forensic science, but I got exposed to and am getting more interested in biostatistics as well.
In forensic science, a common scene is that we get some genetic data from the crime spot and compare it with that of the suspect to see if the two profiles match. This is a much more complicated task that it sounds because a lot of related questions need to be answered before we could draw conclusions from data analyzing. For instance, there are different types of genetic data we could use, do we use STR (short tandem repeats) or SNP (single nucleotide polymorphism) data? What do we consider as a “match” between two profiles? What is the probability that a random non-donor’s DNA happen to match the crime scene type? Previous work has been on done using STR data. The project I was working on is to look at the SNP data and calculate match probabilities using those SNPs. We could get SNP data from human’s autosome, Y-chromosome and mitochondria. Each of the three profiles behave a little bit differently through inheritance so we want to know if the three profiles are independent or have some dependency. This is an interesting question because if we knew their independency, we would be able to get the joint match probability simple by multiplication, i.e. the match probability at AYM would be equal to the product of match probability at A, Y, M each.
Most of the work was done using R programming, which was the challenging part for someone without much programming background. Not having any knowledge in coding, writing loops in R was hard for me at the very beginning. But later on as I was getting more comfortable using R; I came to enjoy coding and thought it was a lot of fun putting calculations and data sorting into loops. With the help of R programming, a large amount of data could be handled easily and neatly and present us with results in statistical summaries and plots, which made it much easier to interpret the data. Programming is a very powerful tool, especially when we deal of lots of data and having a sound skill in programming could be very much helpful in scientific research.
I am very grateful for Howard Hughes Medical Institute and Bryn Mawr College’s kind sponsorship which made this research possible. I am also deeply indebted to the people I worked with in the department. Dr. Weir gave me a lot of guidance and had a lot of discussions with me along the progress of the project. Cecelia Laurie worked on a lot of details with me. She helped me a lot with using R and answered a lot of my questions. Working with them was a really enjoyable experience and the topic I was working on was also very exciting, which all made me now consider pursuing a graduate degree in biostatistics.
(Mentor: Jennifer C. McIntosh, Professor of Hydrology and Water Resources, University of Arizona)
Examining the effects of subsurface hydrogeochemistry on methane productionin the Paleocene-Eocene Wilcox Group of north-central Louisiana
This summer, I conducted off-campus summer research at the Department of Hydrology and Water Resources at the University of Arizona in Tucson, AZ. The research project I purposed involves examining the hydrogeochemistry of formation waters within and above the 2800’ sand formation in the Paleocene-Eocene Wilcox Group in north-central Louisiana (Gulf Coast Basin) to determine controls on microbial methane generation. I am looking to test a hypothesis proposed by Dr. Jennifer McIntosh in a 2010 paper in GSA Bulletin as to why the Olla oil field, which produces from the 2800’ sand of the Paleocene-Eocene Wilcox Group, is a hotspot for biogenic methane production.
Previous research provided evidence of increased methanogenic activity and deemed the Olla oil field a “hot spot” for microbial methanogenesis. The 2800’ sand, an oil and gas-producing formation of the Olla field located approximately 850 meters below the surface, was flooded with CO2 in the 1980s in conjunction with an enhanced oil recovery (EOR) attempt. This EOR project left 9.0x107 m3 of CO2 in the formation and a consequent hypothesis made by Dr. McIntosh attributed this CO2 injection to the increased microbial activity, as microbes can naturally convert CO2 into methane.
My research looks to test and expand on this hypothesis by examining the geochemical characteristics of produced brine and natural gas from sandstone formations in the Wilcox Group (including the 2800’ sand) both in and outside of the Olla field. The goals of this research are to determine if there are factors inhibiting methanogenesis in the formations outside of the Olla field, and if there are other hydrogeochemical factors attributing to increased microbial activity in the Olla field. Typical hydrogeochemical trends that are indicative of methanogenesis include low acetate concentration, no detectable sulfate, high dissolved inorganic carbon (DIC) concentration, high alkalinity values, and low levels of Calcium and Magnesium due to calcite precipitation.
The field site spans a 90-km northwest to southeast transect of north-central Louisiana Twenty-one formation water and gas samples from the Wilcox Group were collected from 6 oil fields in July 2012 to follow up on 2006 and 2011 sampling by Dr. McIntosh’s research group and will be used to provide a comprehensive overview of the hydrogeochemistry of the Wilcox Group.
Initial results show higher alkalinities (up to 57.7 meq/kg, averaging 35.1 meq/kg) in the Olla 2800’ sand compared to formation waters in the 2800’ sand outside the Olla Field (up to 13.8 meq/kg in the Colgrade Field, averaging 9.2 meq/kg). Chloride concentrations increase moving from the NW (averaging 567 mmol/L in the Crossroads field) to SE (averaging 1896 mmol/L in the Cypress Bayou Field). This was expected since the Wilcox Group dips to the Southeast at roughly 264 m/km, and chloride concentrations typically increase with depth. δ13C values of DIC are highest in the Olla Field (26.0‰ VPDB). However, there does not seem to be any discernable trend for the δ13C values of DIC radially away from the Olla Field. A continuing comprehensive analysis involving gas isotopes, water isotopes, and major ion and trace metal chemistry is currently underway.
Determining hydrogeochemical trends that indicate methanogenesis is invaluable as the world increases its reliance on natural gas relative to other fossil fuels such as coal. With better understanding of the factors that either stimulate or inhibit the production of methane, we will be able to better evaluate choices of exploration targets for the safe extraction of this cleaner natural gas.
(Mentor: Dr. Navid Madani, Department of Cancer, Immunology and AIDS at Dana-Farber Cancer Institute and Harvard Medical School)
Discovery of Novel Small Molecule Inhibitors of HIV-1 gp120-CD4 Binding using Click Chemistry and Virtual
Thanks to the Howard Hughes Medical Institute funding, Science Horizons award and Dr. Judith LaLonde’s guidance, I was able to intern as a student researcher for Dr. Navid Madani in the Department of Cancer, Immunology and AIDS at Dana-Farber Cancer Institute (DFCI) for Harvard Medical School and DFCI this summer.
Human immunodeficiency virus, also known as HIV, is a disease that has been affecting millions of people for over 30 years, and has been one of the biggest areas of research ever since. Categorized as a lentivirus, a subtype of retroviruses, HIV’s ability to infect cells, contaminate, replicate rapidly, and maintain a constant change in DNA with every viral entry is what has kept scientists on their toes when trying to understand its functionality. Here at DFCI, the Department of Cancer, Immunology and AIDS specializes in researching one of the most common worldwide pathological HIV-1 strains, group M CF2 family. Within this group of scientists, Dr. Navid Madani focuses on the viral entry aspect of different HIV-1 group M subtypes aiming at the discovery of inhibitory compounds. Working with these compounds was precisely my main focus.
The mechanism of cellular HIV-1 viral entry is quite complex. Its viral spike is composed of three gp120 glycoproteins attached to three gp41 transmembrane molecules (1). The entry of the virus into the cell is initiated when gp120 interacts with CD4 receptor and a co-receptor that causes a conformational change in gp120 allowing the virus access to the cytoplasm of the cell (2). It is this change in gp120 that initiates the viral infection and is its inhibition to this change a target in this research.
Previous studies have shown that the site on HIV-1 gp120 that binds to the CD4 receptor is a non-neutralizing HIV-1 site for antibodies (3). CD4BS antibodies have been characterized and the co-structure of two have been found: F105 and b13 (3). Using one of these antibodies, F105, Dr. Judith LaLonde at Bryn Mawr College was able to identify 38 compounds through virtual screening. I assayed these compounds for the capacity to mimic the F105 antibody and viral entry.
A total of five experiments were done to test this hypothesis, and fortunately 13 compounds out of the 38 were isolated for further analyzing. For the 38 compounds luciferase assays were conducted using two types of viruses, JRFL and AMLV as a control, on R5T4 cells. An experiment design of four concentrations per compound was done at first in order to facilitate the decision of the compounds to be reassessed later on. A total of six concentrations were then used after that first experiment for more detailed data acquisition of the selected compounds. On both cases, the p-luciferase worked as a fluorescence detector in the virus, facilitating the viral infection readings done after lysing. The readings would then provide the count of the number of viruses that infected the cells based on this luminescence. A decreasing number of counts from low to high concentration of compound would indicate inhibitory trend.
Working in this lab was a truly enjoyable experience. This project was a great way to integrate myself to the large-scale work-taking place at this lab while also helping me understand the logistics of a portion of HIV-1 strains. Although it is the case with all research, the ambiguity of not knowing what to expect was what I loved the most. It kept me eager to keep experimenting, and with the help of Dr. Navid Madani, plan what to do next. The experience of feeling like a scientist was definitely apparent throughout my time here, and it is something that is crucial in my practice for future career decisions I make.
Working with HIV has been so far the best experience I have had in my repertoire of research experiences. It is a very interesting and invigorating area to study due to its vast number of strains and complicated way of working. It was more than a pleasure to be able to work with one of the most challenging diseases of which many scientists are devoting their lives to, working hard to understand, and potentially discovering a cure.
Lastly, taking part in this research has made me feel much more confident and happier than ever in my decision to study HIV-1 as a topic for my senior research. I was aiming to do something that I truly enjoyed, and this criterion has definitely been met and surpassed during the course of this summer. I cannot thank Dr. Judith LaLonde enough for guiding me towards a successful summer and hopefully academic year. I would also like to thank Dr. Navid Madani for not only providing me with this amazing opportunity, but also being an outstanding mentor—one who was very supportive of my decisions and helped me meet more professionals in the field I intend on entering after Bryn Mawr.
Reference:
- Pancera, M et al. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility. PNAS 2010, 107, 1167-1171.
- Clapham, P.R.; Repik, A. Plugging gp120s Cavity. Structure 2008, 16, 1603-1604.
- Chen, L. et al. Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120. Science 2009, 326, 1123-1126.
(Mentor: Dr. Chang-Gyu Hahn, Department of Psychiatry, Hospital of the University of Pennsylvania)
Glucocorticoid Receptor Translocation in Depressed Individuals
Major depressive disorder is a significant mental health issue that causes difficulty concentrating, fatigue, hopelessness, irritability, anhedonia, and in extreme cases, thoughts of and attempts at suicide. A significant portion of individuals with this disorder experience hyper-secretion of stress hormones, including adrenocorticotropic hormone (ACTH) and glucocorticoids. This is caused by hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis. In healthy individuals, the HPA axis uses a rapid negative feedback loop to effectively terminate the body’s normal adaptive response to stress. However, some research has suggested that this feedback loop could be defective in depression.
A potential explanation for this dysregulation is a lack of the glucocorticoid receptor translocation in the neurons of depressed individuals. This summer, I was given the opportunity to work in a lab in the Department of Psychiatry at the University of Pennsylvania that was investigating this theory. Earlier findings in this lab had shown that in depressed individuals, there was decreased translocation of the glucocorticoid receptor in olfactory neuroepithelial cells obtained from patients. One of my tasks this summer was to expand the data set by selecting and growing additional cell lines for assessment of .glucorticoid receptor translocation.
The diathesis-stress model is often used to describe the etiology of depression. Based on this model, depression is caused by a natural predisposition to the disorder and an added environmental stressor. Another aspect of my project was to utilize a mouse model to better understand which aspect of this model is affected by attenuated GR translocation. In this part of the project olfactory tissue was obtained from mice subjected to a social defeat paradigm in which they were subjected to chronic stress, which allows them to be separated into groups of stress vulnerable and stress resilient mice as measured by social avoidance behaviors. In this model chronic treatment with antidepressants eliminates this avoidance therefore allowing stress vulnerability to act as a model of depression. Using this model, I cultured the olfactory neuroepithelial cells collected from these mice . The goal of the experiments was to use the mouse model to test the question of whether attenuated GR translocation as seen in depressed individuals is due to a natural predisposition or to the stress that caused the disorder. Preliminary data on GR translocation and the components of the GR chaperone complexes was obtained.
Data from the full group of mice was still being collected at the end of my time in the lab over the summer.
Another opportunity I was given this summer was being involved in the preparation of an application grant through a private foundation which funds research in Autism. Recent research has indicated an etiological role of genetic variations of cadherins in a subgroup of autistic patients. A cadherin is a transmembrane protein that aids cell-cell adhesion in a calcium dependent manner. This protein is particularly interesting when considering that cadherin based cell-cell adhesion is well known to play a key role in CNS development. My portion of this project involved developing a cell-cell adhesion assay that can be used as a functional readout of cadherin dysregulation.
(Mentor: Dr. Corey S. O’Hern, Department of Physics and Mechanical Engineering, Yale University)
Granular Packing of Artificial Rod Piles and Natural Bird Nests
This summer I participated in the research under Professor Corey O’Hern and his Ph.D student Thibault Bertrand on the topic of random packing of rods within certain space. One focus of O’Hern group at Yale University is to understand glass and jamming transitions in granular particles with both computer simulations and experimental set-ups, and the packing of rods is a case of granular particles with especially high aspect ratio. This research is also inspired by the construction of birds’ nests in nature with branches (rods) and the idea was conceived jointly with ornithologist Richard Prum at Yale Peabody Museum of Natural History.
Granular materials like spheres and particles with a low aspect ratio usually require boundary conditions (walls) to maintain their stability. For example, marbles in a container will spread out if the container is removed. For particles with a high aspect ratio like branch sticks, however, their granular packing can remain undisturbed if their aspect ratio satisfies certain conditions. Specific boundary conditions for strong stability, weak stability and none stability are found by experiments, according to researchers Scott Franklin and M. Trepanier at the Rochester Institute of Technology.
My goal this summer is to study the phase transitions of piles of rods. The rods are randomly distributed in a cylindrical container without any pressure. A shaker is constructed under the container and signals of vibration are sent to shake the container through a Matlab program from a sound card in a computer. Different time intervals, frequency and amplitude are applied and a camera takes pictures to measure the height of the rods pile. Different behaviors of rods packing are recorded and analyzed.
Besides, in order to study the 3D structure of bird-nest packing, pictures of different bird nests are taken from different angles and we use Chan-Vese algorithm to detect the edge of the pile shape. In the future, the 2D pictures will be put together to reconstruct the 3D nest and the position of each stick will be studied in order to understand the behavior of granular packing.
During the summer time at Yale, I developed my basic skills to code both in Matlab and C++ and learned some interesting physics research findings by reading papers. I was also exposed to the work of many different laboratories in physics, biology, mechanical engineering and material science engineering department. It was an exciting experience to know about the edge-cutting researches and to talk to brilliant and experienced researchers. It has been a truly rewarding and interesting experience to conduct this summer research.
(Mentor: Dr. Feng Liu, Department of Mechanical and Aerospace Engineering, University of California, Irvine)
Analysis of Induced Flow by Synthetic Jet and Plasma Actuation Using 2D Navier-Stokes Equations
Thanks to the support of Howard Hughes Medical Institute. In this past summer, I got an opportunity to spend 10 weeks at the Department of Mechanical and Aerospace Engineering at University of California, Irvine. Under the instruction of my mentor, Professor Feng Liu, I got exposed to computational fluid dynamics (CFD) for the first time. My research mainly focuses on the general use and application of CFD, and the analysis of induced flow by synthetic jet and plasma actuation using 2D Navier-Stokes Equations. Throughout this summer research, not only did I acquire much knowledge on computational fluid dynamics, but also experienced what it is like to be a research student and inspired me to think about go into this field after college. Afterwards, I spent another 3 weeks at the Hong Kong Polytechnic University for a workshop on aerodynamics and heat transfer for modern gas-turbine engines instructed by Professor Feng Liu. The workshop has taught me the fundamentals and practical applications of fluid mechanics, thermodynamics and heat transfer for use in modern gas-turbine engines for power generation and propulsion. All of those have made my summer a truly rewarding and fruitful experience.
I spent the first few weeks learning the basics of computational fluid dynamics. I got to know that computational fluid dynamics, abbreviated as CFD, is a branch of fluid mechanics that uses numerical methods and algorithms to solve and analyze problems that involve fluid flows. Computers are used to perform the calculations required to simulate the interaction of liquids and gasses with surfaces defined by boundary conditions. Computational fluid dynamics is wildly applied in a number of different fields, including but not limited to aerospace engineering, material engineering, biological engineering and geophysics. Even in economics, computational methods for the study of dynamic economies are wildly used to solve dynamic stochastic nonlinear economic model. The fundamental basis of almost all CFD problems is the Navier-Stokes equations, which arise from applying Newton’s second law to fluid motion, together with the assumption that the fluid stress is the sum of diffusing viscous term and pressure term. The methodology of CFD usually involves preprocessing, simulation and postprocessor. The preprocessing part usually includes the definition of the geometry of the problem, creation of mesh, definition of the physical modeling as well as boundary conditions, etc. The equations are solved iteratively as a steady-state of transient in the second part, the simulation process. And afterwards, a postprocessor is used for the analysis and visualization of the resulting solution.
After acquiring all of those backgrounds knowledge, I started my project on the analysis of induced flow by synthetic jets using 2D Navier-Stokes equations. The motivation of this project came out of the goal of active control. The efficient active control could help us better control the flow of the fluid, but before that, we need to understand the reaction and performance of the fluid by setting different parameters. In other words, only with a good understanding of the feedback of various inputs can we control the system to wherever the direction we want it to go. There are many kinds of controls. In this research, I mainly looked up the velocity distribution as well as the shear stress distribution of the flow induced by synthetic jet and plasma actuation.
In assistant with ANSYS FLUENT, a software that contains the broad physical modeling capabilities needed to model flow, turbulence, heat transfer, and reactions for various industrial applications, I set up a model of a 2D flat plate. Assuming the flow is incompressible and laminar, I first checked my code and set up with Blasius Equations. Then, I added synthetic jets to the main flow with the form of in both vertical and horizontal directions. After running the FLUENT to make it converge, the result shows that in either vertical or horizontal direction, X-velocity of the induced flow reaches its maximum when the synthetic jet is at its highest magnitude at t=2/4 T and its minimum when the synthetic jet has a magnitude of 0. The induced jet at other times ranges between these two extremes. In addition, flows that locate immediately downstream after the inlet of synthetic jet attains the highest X-velocity. In contrast, flows that locate upstream which are farthest from the inlet of synthetic jet are the ones that stays almost stationary.
After that, another study based on plasma actuation was conducted with the model formed by Shyy, Jayaraman and Andersson. In this study, I used FLUENT to model the plasma generation in an asymmetric plate. The device used is a capacitive coupled radio frequency discharge plasma generator, placed on the surface of a dielectric circuit board with the electrode strips on the top and bottom. In this study, a computational framework based on phenomenological electromagnetic model, in conjunction with the Navier-Stokes equations, is developed to investigate the fluid flow, in which the paraelectric force is modeled as body force. The result has shown that the effect on the various regions of the fluid flow can be seen from the velocity profiles. In accordance with expectations, the maximum peak value of the velocity is obtained downstream of the electrode. The overshot of the velocity above the free stream velocity gives the extent to which the plasma affects the flow. Other than that, the plasma produces the maximum relative effect on the velocity profile for the case with the lowest value of the free stream velocity. On top of that, the peak velocity increases with the electrode frequency and voltage, which can be attributed to the linear dependence of the body force on the applied frequency and voltage.
Later on, Professor Feng Liu kindly offered me another opportunity to attend a related workshop. The aerodynamics and heat transfer for modern gas-turbine engines workshop at the Hong Kong Polytechnic University has further more equipped me with some basics of fluid dynamics. The aerodynamics workshop provides a unified approach to internal aerodynamics that deals with fluid flow and thermodynamics of gas-turbine engine, sub-systems such as fans, propellers, compressors, turbines, inlets, and nozzles. Compressibility, rotational, viscous, turbulence and other complicated effects have also been discussed. The cycle analysis and performance of common modern aircraft engines – ramjet, turbojet, turbofan, turboprop, and turbo-shaft engines were also examined, including discussions on cycle innovation and some new types of engines. The heat transfer workshop deals with the important aspect that high-performance gas engines require high inlet temperature in excess of 1700K, and more closely approaching 2000k. Not only new materials of construction are required on rotation blades that can withstand the thermal stress under the high temperature, they have to withstand also stresses induced from rotation/centrifugal and aerodynamic loading, therefore advanced cooling technologies are badly needed for the rotating turbine blades and the stationary vanes. The course mainly focuses on the advanced cooling technologies include, but not limited to, convection, jet impingement, film cooling and transpiration. Experimental methods and numerical modeling have also been discussed.
It was my great pleasure and fortune to have Professor Feng Liu to be my mentor, whom held my hands and introduced me to the world of fluid dynamics. I would like to express my sincere gratitude for Professor Feng Liu and Dr. Juntao Xiong whom have granted me this precious opportunity to conduct research as an undergraduate international student, and have showed strong support and patience along my research. I benefited so much from them not only in terms of knowledge, but also the altitude towards work and life. Other than the research itself, I also interacted with many PhD students on a day-to-day basis. All the people, including me, in our lab are international students from all parts of the world such as China, Thailand and Finland. I learnt a lot about their own country and experience, as well as their PhD life by chatting with them. Their rigorous and considerate way of thinking has also inspired me a lot.
All of those have made this research such an unforgettable experience.
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