REU Projects for Summer 2014 These 37 areas for research projects are proposed for 2014 REU Fellows. Descriptions of these project areas follow below. The 2014 Application and Project Descriptions are also available by email from the REU Director, Associate Dean Martha Absher, at mabsher@duke.edu. Please note that these descriptions are general and describe the research area which you will learn about and observe as part of your educational experience here at the Pratt School of Engineering. For some of those project areas which have been offered previously, brief descriptions of some former Fellows' projects are presented. The 2014 REU Application and 2014 REU Project Descriptions will be available online at: http://www.pratt.duke.edu/reu/absher Project #1: Engineering Gene Expression Systems for Tissue Regeneration Advisor: Charles Gersbach, Assistant Professor, Biomedical Engineering The Gersbach laboratory is dedicated to applying molecular engineering to the development of novel approaches to gene therapy and regenerative medicine. A central focus of this research involves engineering proteins that coordinate changes in cellular gene expression or genome sequence. This research involves enhancing the activity of proteins that occur naturally or engineering entirely artificial proteins to perform these functions. These proteins are then delivered to cells, either by genetic engineering or other drug delivery vehicles, to coordinate complex changes that control cell behavior. One example of this research involves using these proteins to engineer readily available cell types, such as skin cells, to regenerate diseased or damaged tissues, including bone, muscle, or blood vessels. Another example involves using the engineered proteins to correct the genetic mutations associated with hereditary diseases, such as muscular dystrophy and hemophilia. In this project, the student will be challenged to design these new proteins with advisement from the advisor and graduate students. The student will then build the DNA sequences that encode the gene for the protein, including the appropriate gene expression system. If successful, the student will have the opportunity to test the activity of the engineered protein in cultured human cells. Through this research, the student will gain expertise in important laboratory methods, including plasmid DNA propagation and purification, molecular cloning and DNA recombination techniques, electrophoresis, and potentially mammalian cell culture including liposomal transfection for genetic engineering. Additionally, they will gain exposure to the fields of molecular medicine, gene therapy, and regenerative medicine. Michelle Rousseau, Senior, Biochemistry and Molecular Biology and Chemical Engineering, Unviersity of Massachusetts-Amherst Mentors: Dr. Charles Gersbach, Ph.D, Assistant Professor, Biomedical Engineering and Tyler Gibson, Ph.D student, Biomedical Engineering Project Title: Patterns in Myf5 and Myogenin Expression throughout Myogenesis in Mouse Muscle Cells The intent of my study is to understand skeletal muscle lineage commitment for purpose of regenerating skeletal muscle cells in patients who experience myodegeneration disorders, such as Muscular Dystrophy. Previous research has shown that a double knock out in transcription factors MyoD and Myf5 has resulted in a loss of skeletal muscle formation, while single null mutations in either MyoD or Myf5 result in normal muscle physiology and morphology in mice. Since much work has already shown that overexpression of MyoD activates myogenin expression, a transcription factor that commits a muscle cell to myogenesis, my goal is to understand mRNA expression patterns of MyoD’s projected equivalent; Myf5. Through the use of single cell fluorescent in-situ hybridization, I have noted that mRNA expression of Myf5 is most prominent during proliferation of myoblasts and in the early stages of myogenic differentiation. Although Myf5 decreases significantly as myogenin expression appears in the later stages of myogenesis, my data has revealed that the two genes are not completely mutually exclusive of one another. Previous analysis of Myf5 and MyoD protein levels during the cell cycle reveal that they are anti correlated during the cell cycle, thereby supporting my data regarding the significant decrease in Myf5 expression during the later stages of myogenesis. Project # 2: Electric field mediated gene delivery Advisor: Fan Yuan, Ph.D., Professor, Department of Biomedical Engineering Gene delivery into cells depends on its transport across cell membrane and in the cytosol. Intracellular transport of DNA is a complicated process and can be affected by various barriers in cells as well as molecular properties of DNA. To this end, our research projects are focused on experimental measurement of electric field mediated gene delivery and development of mathematical models to numerically simulate the transport processes. Madeline Wilson, Junior, Biomedical Engineering, University of Virginia Mentor: Dr. Fan Yuan, Professor, Department of Biomedical Engineering Project Title: Determining the Elastic Modulus of the Trabecular Meshwork via a Numerical Simulation of an AFM The trabecular meshwork plays an important role in physiological mechanisms of the eye. The aqueous humor is produced in the ciliary epithelium migrates through the eye and flows out into the episcleral vein through the trabecular meshwork and Schlemm’s canal. The equilibrium between production and drainage is necessary to regulate and maintain a normal intraocular pressure. Previous studies have shown that a stiffer trabecular meshwork is associated with patients with glaucoma because the resistance of the tissue causes an imbalance in the intraocular pressure. The stiffness of the trabecular meshwork can be predicted using force-indentation data collected from an atomic force microscopy in concert with a mathematical equation, known as the Hertz model. It is necessary to determine under what conditions, if any, the Hertz equation serves as a valid model for predicting the stiffness of the trabecular meshwork. Here I show that the Hertz model is indeed an accurate model from which we can determine the Young’s modulus of the TM given data produced from an atomic force microscopy when the TM experiences indentation ranging from 0 to 0.6 um. This deformation is typically associated with an applied force of 0 to 0.12 nanonewtons, the latter being 0.03 nanonewtons from the maximum force experienced in the AFM. I found that the thickness of the TM greatly influenced the ratio of the predicted Hertz value and the simulated value, determining that the model is within 20% accuracy of predicting the stiffness with a thickness greater than 40 um. The biggest discrepancies in values between the numerically simulated data and the Hertz model calculation can be attributed to the location of the microsphere on the TM and the influences of surrounding ocular substructures, a less stiff TM or a smaller value of Young’s modulus, and a smaller height or thickness of the TM. This data is important because it ultimately allows for a more accurate determination of the stiffness of the trabecular meshwork by rejecting the Hertz equation as a valid model when deformation exceeds 0.6 micrometers. This accuracy and validity will elucidate information about the relevance of a stiffer trabecular meshwork in the eye and certain ocular diseases, specifically glaucoma. Jazmine Brown, Junior, Biomedical Engineering, North Carolina A & T State University Mentors: Fan Yuan, Ph.D, Professor and Jianyong Huang, Ph.D, Postdoc Fellow Project Title: Electrotranfection of DNA into Tumor Cells Electroporation is a process where rapid pulses of electrical potential are applied to cells suspsended in medium. This electrical potential causes the cell membrane to break down and pores to form. These pores allow for the delivery of drugs or genes as well as the delivery of small molecules such as chemotherapy or the delivery of macromolecules such as DNA. There are four major components to the elctroporation process: The voltage, the pulse duration, the number of pulses, and the interval length. The ideal conditions for electroporation process are short, high frequency pulses or long, low frequency pulses. In order to make the transfection of DNA more efficient, it was hypothesized that this could be achieved by combining the ideal conditions as well as increasing the interval length of the pulses. Three different parameters were used combining a difference in interval length as well as the ideal conditions. A 170 volt pulse with a pulse duration of 10 milliseconds was used as the base parameter. For the short, high frequency pulse, 180 volts and a pulse duration of 5 milliseconds was used. For the long, low frequency pulse, 160 volts, with a pulse duration of 15 milliseconds was used. All three of these parameters proved that the cells exposed to the pulses with longer interval lengths had a greater amount of transfected DNA. More research will be done with determine how and why this phenomenon occurred. Jason Hallo, Biology Major, Gallaudet University Chemotaxis Velocity Mentors: Dr.Fan Yuan, Professor of Biomedical Engineering and Dilip Nagarkar, Pratt Fellow, Biomedical Engineering Jason Hallo is a biology major from Gallaudet University. Jason’s project focuses on chemotaxis velocity of bacteria. Gene therapy might one day cure cancer in our cells. Unfortunately, gene therapy when placed into a virus is not able to host into a person’s DNA. An alterative method of gene therapy is to use bacteria instead of viruses. Bacteria can’t get in the host but they are able to give proteins that hopefully will regulate cancer cells one day in the future. An understanding of bacteria E-coli’s mobility is required before we can do further experiments on gene therapy. My project aimed to study and understand the mobility of bacteria E-coli in the presence of four different concentrations of dextrose. Charts of results are made based on the experimental measurement of the rings of growth of the bacteria on the petri dishes. Our finding was that bacteria move more when there is a lower concentration of dextrose present. These findings will be used in further experiments in the laboratory on the development of gene therapies using bacteria. REU Fellow: Kelley Bohm, Bioengineering Major, Pennsylvania State University Protocol for Microfluidics Tumor Formation Kelley Bohm is a bioengineering major from Pennsylvania State University. Her project focuses on Microfluidics, which offers a novel way to observe interactions between therapeutic bacteria and cancer cells. Culturing the cancerous tumors in microscopic conditions allows for precise manipulation of the cells and the bacteria that will be introduced. Creating these tumors, before the bacteria are even introduced, is a complex process that needed to be worked out in order to move on to more complex topics. Cells need to aggregate effectively within the microfluidic chamber and this involves proper flow rates, cell concentrations, and possibly a substance to help aggregation. One potential aggregate that was considered was poly-L-lysine. This was first imaged with cells to choose the concentration that yielded the desirable amount of aggregation and then the viability of this mixture was tested using trypan blue stain. The ideal amount – 20% poly-L-lysine – was determined to be too deadly to the cells and will not be used. Collagen will be considered in the future. Many trials were needed to determine the ideal flow rates and cell concentrations. The specific numbers are detailed later in this paper. This data was compiled and a protocol was made for Dr. Yuan’s lab and others to use for microfluidic tumor culturing. REU Fellow: Danielle F. Garcia, Chemical Engineering, University of New Mexico Developing a Multicellular Layer Model for Drug Diffusion in Tumors Danielle is a chemical engineering major from the University of New Mexico. Her project involved drug diffusion in tumors. An in-vitro model for drug diffusion through solid tumors has been developed. The development process is comprised of growing a three-dimensional cell culture on a collagen coated Teflon membrane suspended in stirred media for up to 12 days. HT-29 human colon carcinoma cells and B-16 murine melanoma cells were used to demonstrate the procedure in developing these multicellular layers (MCLs). HT-29 cells have been shown to produce an MCL thickness of 160mm after 12 days in suspension. A comprehensive investigation was carried out of variables affecting growth of B-16 MCLs to achieve maximum reproducibility and comparability to HT-29 MCLs. We aim to generate a sufficient amount of MCLs, and refine the development process to visualize common properties of tumors such as necrosis and hypoxia, which affect diffusion properties. These MCLs can then be used in further studies of drug transport to aid in cancer treatment research. REU Fellow: Rebekah Lee Smith, Biology Major, Gallaudet University Project: Quantification of Electrical Impedance of Tumor Tissues Rebekah's project was in biomedical engineering and its application in cancer research. The goal of her project was to develop a method to determine changes in the volume fraction of cells in tumor tissues based on electric impedance measurement. This method can be used directly in the clinic to monitor the efficacy of any anticancer treatment. In her experiment, different electrodes were used to measure the impedance as a function of electric field frequency in tumor tissues. The impedence was then converted to the resistance, capacitance, and inductance of tumor tissues based on the Cole model. The tissue used in this experiment was a rat tumor, called rat fibrosarcoma. The volume change of tumor cells was induced by a mannitol solution that would in theory shrink tumor cells due to the osmotic effect. The cell shrinkage was detected through electric impedance measurement and data analysis based on the Cole model. After several sets of experiments on fibrosarcoma, Rebekah did find that the mannitol solution made the cells shrink, and the final impedance graph did fit into the Cole model. Rebekah completed the formulas for resistance indicating how the tumor reacted and shrank in the mannitol solution. Therefore, her hypothesis that fibrosarcoma cells would shrink in the mannitol solution was proved true. REU Fellow: Daniel Lundberg Project: Viscous Polymer Solutions for Sustained Drug Delivery Daniel Lundberg is a senior biology major at Gallaudet University. He performed his research under Dr. Fan Yuan, Assistant Professor, and Yong Wang, graduate student in the Department of Biomedical Engineering. Daniel’s research focused on a novel method to treat cancers and tumors via targeted drug delivery systems. As traditional methods and local drug delivery lead to the dissemination of the drug into the systemic circulation, the side effect impact of a cancer treatment increases. Temperature-sensitive polymers offer a possible method in containing the drugs within the tumor, reducing the side effects. In order for a substance to be a successful polymer for this treatment, it has to have a low viscosity at room temperature yet a high viscosity at body temperature. Polymer solutions, such as alginate, calcium ion/alginate, Poloxamer, PNIPAAM, and methyl cellulose polymer solutions were tested as potential agents which can reduce drug clearance into the systemic circulation and improve drug retention in tumors, reducing the side effect of the anti-tumor drugs. From the data, it was clear that the alginate and methyl cellulose polymers did not attain the goal, since they were more viscous at room temperature than body temperature. Certain concentrations of PNIPAAM and Poloxamer polymer solutions turned out to be promising polymers. Their viscosity had dramatic increases from room temperature to body temperature, achieving the goal. The ionic environment variable proved to be effective in increasing a polymer’s viscosity at a certain concentration. The next step of this experiment would be to focus on the addition of the calcium ions to the successful polymers to observe the results. Also, the promising polymers need to be tested in mice with the aid of fluorescent drug markers to observe the progression of the polymer/drug markers. Daniel learned challenging new laboratory techniques in this project. Project #3: Advanced Biophotonic Structured Illumination Imaging System Design Advisor: Joseph Izatt, Professor, Biomedical Engineering Professor Izatt’s laboratory has REU opportunities in a project entitled “Advanced Biophotonic Structured Illumination Imaging System Design.” The goal of this project is to apply cutting-edge signal and image processing techniques to improve the resolution of conventional optical imaging devices such as microscopes and ophthalmoscopes. This will be done by designing novel laser lighting patterns to illuminate cells and tissues with special patterns of light which are designed to reveal fine structures upon collection and image processing. This approach will contribute directly to the design of diagnostic instruments capable of imaging individual photoreceptor cells in the living human retina. Students involved in this project will gain experience in medical imaging laboratory practice, optical system design and prototyping, computer interfacing with laboratory instrumentation, and image processing algorithm design and programming. Students will also interact directly with physicians on identifying requirements for instrument design and in testing of prototypes. Olivia Sutton, Junior, Biomedical Engineering Major, Washington University in St. Louis Mentors: Dr. Joseph Izatt, Professor, Department of Biomedical Engineering and James Polans, Department of Biomedical Engineering Project Title: Wavefront Aberrations along the Horizontal Meridian in Human Retinas The existing model of the human eye remains incomplete. The optical quality of the human eye on-axis has been well-investigated, but we are interested in revealing the performance of the human peripheral optics. In order to do so, we built a Shack-Hartmann Wavefront Sensor and developed supporting software and image processing techniques in order to measure radial aberrations. Our physical sensor required careful setup and calibration before usage on a human subject is appropriate. The supporting software was developed to optimize the data collection process, and it was written in conjunction with the ImagineOptics HASO SDK. We used compressive sensing in data collection and processing in order to increase our camera speed without any necessary hardware improvements. Our instrument, when finished, will have the potential to collect a much wider scope of data than previously attained by any group, and at a much more rapid rate. Theresa Meyer, Sophomore, Computer Science Engineering, Princeton University Mentors: Dr. Joseph Izatt and Dr. Sina Farsiu, Dept. of Biomedical Engineering at Duke University Project Title: Optical Coherence Tomography (OCT) with XFast/YFast Imaging High resolution volume images of the retina can be taken using a technique called Optical Coherence Tomography (OCT). Capturing this volume can take four seconds or greater, and in this amount of time a patient’s eye has the ability to move and cause jumps and distortions in the image, known as motion artifacts. These motion artifacts make it more difficult for ophthalmology professionals to diagnose and treat diseases of the retina, such as glaucoma. However, many software algorithms have been developed to try to fix these motion artifacts after the volume has been captured. One such software-based program that repairs motion artifacts was developed in the lab of Dr. Fujimoto of the Massachusetts Institute of Technology, known as XFAST/YFAST. This paper provides an evaluation of this algorithm. In order to analyze this algorithm, it must be recreated. One hurdle in this study lies in that the XFAST/YFAST paper was studied to replicate the algorithm, and the exact code used by Dr. Fujimoto is not available. Therefore, replication of the exact code utilized is lacking and similarity is only based on results of a completed program. It is known that in XFAST/YFAST, fixing the motion is done retrospectively by correcting motion on the OCT data sets themselves. Volume scans with orthogonal fast scan axes are registered and then combined in order to form a final, more accurate volume with reduced motion artifacts. This goal can be broken into three main steps: preprocessing, optimizing a cost function, and volume merging. The first of these steps, preprocessing, was successfully recreated in MATLAB. For the second step, optimizing the cost function, work is currently being done. Progress is currently being made on creating a program that is able to detect the displacement of an image when shifted a known number of pixels. Also the multi-resolution optimization, part of the cost function, used in the XFAST/YFAST algorithm has been duplicated. Due to time constraints, work on the volume merging step has not begun. If given more time and the algorithm was successfully recreated, then it would be analyzed for performance and improved upon. Project #4: Cell based disease diagnostics with biophotonics Advisor: Adam Wax, Theodore Kennedy Professor, Biomedical Engineering My research is based on using non-invasive optical techniques to examine biological cells and tissues in a way that is not possible with traditional methods. We have developed several techniques capable of detecting disease at the cellular level using biophotonics techniques such as holography, light scattering and spectroscopy. Currently, we are developing these techniques for application in the clinic and at the point of care. Research in my lab involves designing and implementing electronic and optical systems, programming in Labview for instrument control, as well as signal analysis using C++, MATLAB and CUDA . This project can include hardware (optical and electrical systems) and/or software (Labview, MATLAB and/or C++) components. Project # 5: Cardiac Ablation Imaging with ARFI Ultrasound Advisor: Patrick Wolf, Assistant Professor, Department of Biomedical Engineering The overall goal of the project is to develop a multimodality imaging system to guide cardiac ablation therapy. The system will exploit catheter based acoustic radiation force impulse imaging to characterize lesion growth during ablation. This technology will be integrated into the standard clinical catheter guidance paradigm yielding a complete tool for ablative therapy of cardiac tachyarrhythmias. A student working on this project would be performing ablation experiments in vitro and assisting with in vivo experiments and imaging the outcome with ultrasound. Paige Maxon, Junior, Biomedical Engineering, NC State University Mentors: Dr. Patrick Wolf, Associate Professor Department of Biomedical Engineering and Thomas Jochum, Doctorial Fellow Project Title: Temperature Measurement with Charging Implanted Medical Devices Charging the battery of an implanted medical device is important for long term use and its ability to produce continuous data. It is vital that the charging process does not increase temperature more than 2 degrees Celsius, as that can be a danger to the patient. This experiment involved developing an electrode wand and charging it in a bath of saline water that represents the human body. 12 thermocouples at distances of 0 mm, 2.5 mm, 5 mm, 7.5 mm, 10 mm and 15 mm into the water, were attached to the end of the wand. Temperature readings were taken before, 5 minutes during, and 5 minutes after 500 mA of current was pushed through the water. The wand was also rotated at 60 degree intervals to ensure that thermocouples had an equal distance from the current source wire. Graphical representations can show the small temperature changes from 1 to 3 degrees. The real life application of this experiment would only be using 10 mA of current. This power factor difference of 2000 shows how safe the charging would be for a patient, as the temperature would definitely not rise over 2 degrees. Varying factors involved in the experiment such as thermocouple precision and accuracy and resistor heat exposure could have affected results. Therefore, more experiments should be done in the future to test those confounding factors. Project #6: Engineering Bacteria for Medical Applications Advisor: Lingchong You, Associate Professor of Biomedical Engineering We are engineering bacteria for medical applications by constructing synthetic gene circuits. These projects involve development of genetic sensors that can detect changes in the environment, and containment modules that limit un-intended bacterial proliferation. These projects will expose students to both mathematical modeling and experimentation. The summer student will primarily participate in design, construction, or characterization of synthetic gene circuits. Prior experience in mathematical modeling, cloning, or bacterial growth experiments is preferred. Project # 7: Neuronal circuits in the primate brain and their implications for robotics Advisor: Marc A. Sommer, Dept. of Biomedical Engineering and the Center for Cognitive Neuroscience The primate brain is a network of highly interconnected areas. Most of the areas have been studied at this point, and we know much about them. Little is known, however, about how the areas talk to each other. Somehow their connections form highly synchronized, widespread circuits that mediate our perception, cognition, and movements. The overall goal of my laboratory is to study the interaction of brain areas at the circuit level. Our primary method is to record from single neurons in behaving rhesus monkeys. The animals perform tasks similar to video games that involve visual stimulation, decision-making, and eye movement responses. We study the signals carried by neurons between brain areas while the animals perform the tasks, analyze what the signals represent, and design computer models that help us to interpret our findings and apply them to technology. We are currently designing a model of the visual system that rotates a video camera in a way that approximates real eye movements. Input from the camera guides a robotic arm, and the bioengineering challenge is to design the system so that the arm makes accurate visually-guided manipulations even as the video camera moves around -- just like we are able to inspect and manipulate tools even as we move our eyes around. A good undergraduate candidate for a position in our laboratory would have studied biology (including a basic understanding of neurons), would be comfortable with animal research, and should have familiarity with computer programming (e.g. Matlab or C), engineering, or both. Project #8: (WISeNet): Robotic Saccadic Adaptation and Visually-guided Auditory Plasticity Advisor: Dr. Marc Sommer, Associate Professor, Biomedical Engineering and Dr. Jennifer Groh, Professor, Psychology & Neuroscience (WISeNet) Many items in the world make sounds, so to understand the world coherently biological brains must colocalize visual and auditory inputs. This is important not only for perception, but also for action. If you suddenly hear something next to you, looking at it quickly and accurately could save your life. Sensor fusion and learning based on heterogeneous sensor data, and subject to changing environmental conditions, are very challenging problems that are yet to be overcome in artificial sensor systems. Currently, robotic sensors deployed to perform both sensing and motor or navigation tasks, such as mapping an environment and manipulate objects while avoiding collisions, must first stop and process the sensor data, and then execute the motion. Their ability to process data, and coordinate across different sensor modalities is far removed from that observed in biological systems. The focus of this project is to transfer findings of on-going research on biological sensory systems to the design of artificial robotic sensors. This research will aim at reproducing some of the capabilities of biological sensors, such as, coordinating sensor movements and fusing heterogeneous sensor data, while performing motor tasks, such as, manipulating an object, or moving across an obstacle-populated room. A servo-mounted camera will be used to send the visual input to the robot’s computer (e.g. coffee mug), and the computer must rotate the camera at saccadic velocities. The sensorimotor system will be simulated using a neuronal sheet structure designed with the program Topographica, and the experiment is set up to examine presaccadic remapping, and mediation of our sense of visual continuity while we move our eyes. Research in the Sommer Laboratory involves recording from single neurons and studying the effects of inactivating or stimulating well-defined brain areas. Our goals are to understand how individual areas process signals and how multiple areas interact to cause cognition and behavior. Results from the work are guiding the design of vision-based models and robots. The goal of the REU fellow will be to help test a computational sensorimotor system on a robot comprised of a servo-mounted video camera, microphone, and sound card, soon-to-be equipped with a robotic arm. Project # 9: (WISeNet): Sensorimotor Modeling and Control Advisor: Dr. Marc Sommer, Associate Professor, Biomedical Engineering Dr. Craig Henriquez, Professor and Chair, Biomedical Engineering, and Dr. Silvia Ferrari, Professor, Mechanical Engineering and Materials Science (WISeNet) Recent results in the neuroscience literature indicate that the sensorimotor system functions as a feedback controller that optimizes neuronal representation of behavioral goals, such as, regulatory and exploratory behavior. Several experiments have also shown that exploratory actions, such as, whiskers deflections in rat’s tactile exploration, are optimized for sensory input, and that the adult primary somatosensory (SI) cortex compares the meaning encoded in new sensory inputs with internal representations, or models, of the sensory experience accumulated during a lifetime. For example, an internal dynamic may be used by the brain to represent the behavior of the external environment, as in the case of saccadic adaptation where the frontal eye field may use an internal model of the motor-to-sensory transformation, in combination with the current state of the motor system to predict the sensory input. This prediction may be compared to the actual, reafferent sensory input to inform the brain of sensory discrepancies evoked by environmental changes, and generate shifting receptive fields. Drs. Sommer, Henriquez, and Ferrari are currently collaborating to develop a computational sensorimotor systems comprised of a network of neural networks each representing an internal model and controller, and inspired by their biological counterpart. Their laboratories are investigating the use of biologically-plausible paradigms, such as spiking neural networks and synaptic time-dependent plasticity, to simulate and adapt both the internal models and feedback controllers in the sensorimotor system subject to changing environments and external stimuli. The REU fellow will test intelligent control designs, such as, model-reference adaptive control, temporal difference, and adaptive critics through robotic and computer games conducted in the Ferrari Laboratory, as well as through real-worlds experiments on saccadic adaptation and visually-guided auditory plasticity conducted in the Sommer Laboratory. Kenneth Avilés Padilla, Junior, Computer Engineering, University of Puerto Rico at Mayagüez Mentor: Dr. Marc Sommer Project Title: Reverse Engineering the Brain to Understand the Primate Visual System With the use of a humanoid robot and a neural network, we want to build a computational model of the primate visual system. We would like to incorporate a link between two distinct networks, a network of actuators of the robot and a biologically-based neural network. Our goal is to achieve a seamless connection between the two in a way such that we can create a model that mimics the biological functions and physiological aspects of the visual system using a computational approach. In order to keep the large-scale structure and function of the visual system in consideration, we use the academic software called Topographica. With this software, we can investigate the organization of the visuosaccadic system and the neuronal properties that emerge within it when used for specific tasks. Through the course of this project, I was able to successfully achieve the objective. This consisted of successfully importing the neural network into the robot and having the robot use the neural network as if it was its brain. For example, it successfully follows a red object with it left arm. The robot remains autonomous while exhibiting a fluid behavior when interacting with its environment, much like that of a human. Our work could be a step to a better understanding of the brain. Our results from the computational work will potentially help in the pursuit of more experimental studies. PROJECT #10; Application of Endothelial Progenitor Cells for Vascular Repair Advisor: Dr. George Truskey, Professor,Biomedical Engineering and Senior Associate Dean Endothelial progenitor cells derived from adult and umbilical cord blood represent a promising source of cells for applications in tissue engineering, repair of blood vessels and seeding of vascular grafts, stents and ventricular assist devices. Work in our lab is focused upon determining the properties of these cells when cultured with smooth muscle cells under flow conditions, understanding ways to optimize the dynamic adhesion of the cells and furthering the development of tissue engineering applications. Alexis Bertram, Senior, Bioengineering, Clemson University Mentors: Dr. George Truskey, Senior Associate Dean for Research, and Brittany Davis, Biomedical Engineering graduate student, Pratt School of Engineering, Duke University Project Title: Oxygen Uptake of Skeletal Muscle Cells The aim of this study is to optimize testing conditions to measure oxygen uptake in tissue engineered skeletal muscle cells. Monitoring oxygen consumption as an indicator for functional engineered tissue health may revolutionize how toxicity testing is conducted. Cultured immortalized C2C12 (mouse) skeletal muscle cells were grown in a 2-D layer on a glass coverslip and placed into a custom-made acrylic flow chamber. Growth media was circulated through the chamber and Lucid™ oxygen micro-sensors were used to obtain a 2-point calibration curve of oxygen consumption by the cells over a period of 24 hours. Instech™ pump settings were determined to achieve optimal physiological flow for the system, and preliminary results show that cell viability within the chamber was acceptable for further 2-D and 3-D tissue monitoring. Insufficient data was collected to confirm oxygen sensor compatibility with current project design. REU FELLOW: Kristen Hambridge, Biomedical Engineering Major, North Carolina State University Response of Human Umbilical Vein Endothelial Cells in Co-culture With Aortic Smooth Muscle Cells In vitro cell culture systems are important for modeling diseases such as Atherosclerosis. Atherosclerosis is a disease of the intima, resulting in plaque formation on the inner lining of the artery walls. Low Density Lipoprotein (LDL) accumulation within the vessel wall leads to an immunological response with inflammatory attributes. The increased permeability of the endothelial layer to LDLs has played a major role in Atherosclerosis. The study aims to research the role of human umbilical vein endothelial cells (HUVECs) in co-culture with aortic smooth muscle cells (AoSMCs). Specifically, it aims to discover whether the inclusion of smooth muscle cells will improve the physiological nature of endothelial cells. This was tested by performing albumin permeability tests on a HUVEC monolayer, AoSMC monolayer, co-culture, and the membrane containing no cells. Cells were grown in media containing 3.3% and 10% Human Serum (HS). Permeability was tested on days 2,3, 5, and 7 post seeding. Days 5 and 7 were found to be optimal days. Average albumin permeability for HUVECs was 1.35 +/- 0.47 for 10% HS at Day 5, 0.75 +/.04 for 3.3% HS at Day 5, 1.95 +/- 0 for 10% HS at Day 7, and 1.34 +/- 0 for 3.3% HS at Day 7. Average albumin permeabilities for AoSMCs at Day 5 were 4.05 +/- 0.69 and 1.72 +/-0.62 for 10% and 3.3% HS respectively while Day 7 were 4.95 +/- 1.33 and 5.2 +/- 0.93 for 10% and 3.3% HS respectively. Lastly, the co-culture average albumin permeabilities were found to be 1.97 +/- 0.35 and 0.83 +/- 0.4 at Day 5 for 10% and 3.3% HS respectively while values for Day 7 were .089 +/0.34 and 1.77 +/- 0.66 for 10% and 3.3 % HS respectively. Overall, most permeability values at 3.3% HS were lower than at 10% HS. At day 7, the permeability of the co-culture was lower than the ECs at 10% but not for 3.3% HS. It can be concluded that with time, the ECs respond better in co-culture than alone when in 10% HS. REU Fellow: Viet Le, Chemistry Major, Gallaudet University Project: Interactions between the Endothelial Cells and the Smooth Muscle Cells in Co-Culture: The Endothelial Cells Confluency in Co-Culture The overall project in Dr. Truskey’s laboratory, in which Viet worked, aims to construct a tissueengineered blood vessel and a synthetic (polymer) vessel, so it can be put into a human body that has a clotted vessel. The tissue-engineered blood vessels are made from cells that grow into tissue on a degrading scaffold. Current tissue-engineered blood vessel form clots over relatively short periods of time because the endothelial cells tend to rip off synthetic vessel that clots easier. The endothelial cells need to adhere and function properly in the tissue-engineered blood vessel to prevent clotting. After the smooth muscle cells have grown to a confluent layer on the slideflask, the endothelial cells were seeded and cultured for several day for growth. Antibody Labeling was used to specifically stain cell junction proteins so that the visible cell junction protein appear under the fluorescent microscope. In Viet’s research, attempts were made to stain three type of cell junction proteins: VECadherin, -catenin, and PECAM. VE-Cadherin and -catenin were specifically localized to the inter-endothelial cell junction and PECAM was specifically localized to the outer-endothelial cell junction. Two variables for staining the cell junction proteins which must be considered are (1) the concentration of antibody labeling solution to specifically stain for cell protein and (2) the incubation time. The VE-Cadherin and -catenin antibody did not stain the cell effectively in the endothelial cells monolayer, under all the varying concentrations and incubation times. VE-cadherin and catenin antibody did not show its visible borders where two cells had merged together under the fluorescent microscope. PECAM was considered as the next cell junction protein and the results show that PECAM successfully stained the cell borders alone with concentration of 20 L to 50L PECAM antibody solution in the endothelial cells monolayer. Dapi was added to the PECAM protocol that stains cell nuclei to indicate the visible stained nuclei within each visible PECAM border under the fluorescent microscope. The isotype was used as a control group that should not show any visible cell junctions protein with the same PECAM protocol. Viet hypothesized that the PECAM antibody will stain the endothelial cell borders on the smooth muscle cell. His results showed the PECAM protein did not stain effectively the endothelial cells monolayer at low concentration. For staining the PECAM protein in future investigation, Viet concluded that an increasing concentration of PECAM antibody solution should stain the entire cells in co-culture, and the incubation time must vary with the antibody concentration. Project #11: Development of mRNA Advisors: Kam W. Leong, Professor, BME vaccines for anti-tumor immunity Nanoparticle-mediated delivery of mRNA vaccines warrants attention because of its potential for direct in vivo administration of mRNA vaccines without ex vivo manipulation of dendritic cells. We have previously shown that primary dendritic cells can be efficiently transfected by mRNA encapsulated in nanoparticles. We have also identified intranasal and intravenous routes as optimal vaccination sites, and further characterized associated transfection efficiencies and transgene expression kinetics. In this project, we will investigate the efficacy of intranasal vaccination of mRNA encoding antigen protein for inducing anti-tumor immunity in both prophylactic and therapeutic settings. We envision that the student will assist in the following aspects of the project: 1) Optimize the formulation of mRNA nanocomplexes for transfection 2) Assist in conducting animal experiments; 3) Characterize the immunological response of mRNA tumor vaccination. Krystian Kozek, Materials Science and Engineering Major, North Carolina State University siRNA Delivery Into LNCaP Cells Using a Novel, Multivalent Nanocomplex Mentors: Dr. Kam Leong, James B. Duke Professor, Department of Biomedical Engineering and Dr. Hanying Li, Postdoctoral Associate, Department of Biomedical Engineering Krystian Kozek is a materials science and engineering major from North Carolina State University. His research focues on short interfering ribonucleic acid (siRNA) delivery into prostate cancer (LNCaP) cells, which was attempted using a novel and multivalent nanocomplex. The complex was a three-armed deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) hybrid structure, where the arms were connected through dithio-bismaleimidoethane (DTME) by disulfide bonding. The disulfide bonding of the arms was not as efficient as desired; however, conjugation was successful, although with a low yield. A three-armed and fully formed complex has not yet been completely successful proven; however, preliminary data points towards assembly of the full nanocomplex. Application of this nanocomplex for the receptor-mediated endocytosis into the LNCaP cells has been preliminarily successful, with the aptamer guiding uptake and the siRNA knocking down chosen genes; future research will aim to prove the efficiency and study the application in cancer research. Nevija Watson, Chemical Engineering Major, North Carolina A&T State University Fabrication of Nanopatterned Surfaces to Study Stem Cell Differentiation Nevija Watson is a junior chemical engineering major from North Carolina A & T State University. The hypothesis of her research project over the summer was that cells react to nanotopographic cues under static conditions and flow alters the cells behavior. We wanted to engineer a synthetic surface with topographic cues in the nanoscale to mimic a stem cell niche. We want to use this synthetic niche to expand and differentiate human mesanchymal stem cells for cellular therapies. In my time here over the summer, we found that the topographic cues on the synthetic patterned surface we created do affect the cells. Cells seeded on the patterned surfaces grew and moved along the ridges of the pattern compared to cells seeded on a flat surface which spread out along the surface in a normal fashion. We have found that flow increases the elongation of the cells on the patterned surface and the cells become oriented in the flow direction on the flat surface. Our findings from the duration of my project are still preliminary; there is still extensive research to be done on the reaction of the cells to flow and the nanotopographic cues Project #12: Characterization of peripheral blood endothelial progenitor cells for use in prosthetic vascular grafts Advisor: Dr. William Reichert, Professor, Biomedical Engineering and John Stroncek, and Michael Nichols, Biomedical Engineering Graduate Students Cardiovascular disease is the leading cause of death in the US. Blockage of the coronary arteries is the most deadly form of cardiovascular disease and is one of the main causes of sudden cardiac arrest. One surgical solution for blocked coronary arteries is coronary artery bypass surgery. These bypass grafts are isolated from a patient's mammary artery or saphenous vein. However, this surgery can only be performed if autologous vessels are healthy. Not all coronary bypass surgery candidates have healthy vessels available, and thus there is scarcity of suitable small diameter vessels for patients. Synthetic grafts made out of ePTFE or Dacron have been looked to for a possible replacement of autologous vessels. However, currently synthetic grafts are limited to vessels with an internal diameter larger than 6 mm due to the thrombogenicity of the material. Investigators have attempted to improve the performance of these materials by coating the lumen with endothelial cells, and successful seeding of endothelial cells has been shown to improve the long-term patency of these grafts. Still, major technical hurtles include finding a relevant autologous cell sources and improving the attachment of endothelial cells to prosthetic grafts. This research focuses on isolating a type of high proliferation potential endothelial cells that are found in an individual's circulating blood, called endothelial progenitor cells (EPCs). We are currently attempting to determine whether EPCs represent a viable and easily isolated autologous cell source for the seeding onto synthetic vascular grants. The strength of adhesion and the antithrombotic properties of the EPCs on synthetic graft materials will be determined through in vitro assays. Gene therapy will be used to regulate the expression of antithrombotic molecules. Seeded grafts will eventually be tested in animal models. This project involves cell culture, gene expression analysis, and phase/fluorescent microscopy. Project #13: Tissue-engineered model of muscle disease Advisors: Nenad Bursac, Associate Professor, Biomedical Engineering and Mark Juhas, Biomedical Engineering Graduate Student Duchenne Muscular Dystrophy (DMD) is a debilitating disease that occurs due to lack of the protein dystrophin. The disease effects 1 in every 3500 males and in most cases results in patients being wheelchair-bound by age 12 and dying before age 30 due to respiratory or heart failure. In this project we will apply genetic and tissue engineering methodologies to generate novel tissue model of DMD muscle and by altering expression of membrane-matrix binding proteins (integrins) attempt to decrease cell death, improve force generation capacity, and restore normal myofiber architecture of the DMD muscle. A variety of tissue engineering techniques, gene and protein expression analyses, and physiological tests will be utilized to accomplish goals of this project. Amanda Ipolito, Junior, Biomedical Engineering Major, Worcester Polytechnic Institute Mentor: Dr. Nenad Bursac, Associate Professor, Biomedical Engineering Project Title: Visualizing Inward Rectifying Potassium Channels in Cardiomyocytes Ion channels play a key role in the electrical propagation in cardiac tissue. Serious cardiac arrhythmias can occur due to the disruption of these channels. Understanding how distributions of ion channels, specifically the Kir2.1 channel, change over development and the course of disease is key in understanding the diagnosis process. To visualize the Kir2.1 channels, HEK-293 cells were transfected with Td-tomato fused cardiac potassium channel, Kir2.1, using lentiviral transfection. Ex-293, a HEK cell line which stably expresses the cardiac proteins, Kir2.1, Nav1.5, and Cx43, were also cultured. Immunostaining and microscopy were used to image the Kir2.1 channels. Optimized immunostaining techniques used: 50/50 Methanol acetone (2 minutes), 0.1% Triton-X (30 minutes, chick serum and 1% BSA in PBS (1:5, 30 minutes), goat Kir2.1 anti-bodies in blocking solution (1:200, 24 hours), secondary antibodies in blocking solution (1 hour). Immunostained cells were imaged using confocal and fluorescent microscopes. The optimized technique proved successful in engineered cells and the human heart. Techniques need to be further optimized for stains in neonatal and adult rat heart sections. Leigh Atchison, Senior, Biomedical Engineering, North Carolina State University Mentors: Dr. Nenad Bursac, Principle Investigator and Dr. George Engelmayr, Research Scientist, Department of Biomedical Engineering at Duke University Project Title: Optimizing a Cell Culture Medium for the Expansion of Skeletal Muscle-derived Satellite Cells and Myoblasts In Vitro Skeletal muscle tissue engineering is an exciting field of research that has the potential to solve many medical conditions or injuries resulting in large volumetric muscle loss as in battle wounds or muscle degradation as in muscular dystrophy. The ability to create this muscle in large, cost effective quantities is currently limited. The two critical issues with skeletal muscle engineering are 1) the small number of skeletal muscle derived myoblasts and satellite cells that can be isolated as well as 2) the purity of these cells for skeletal muscle reconstruction. In order to overcome these limitations, we tested different growth environments in order to determine the optimal conditions for maintaining large number of phenotypically pure cell populations. Neonatal rat skeletal muscle cells were enzymatically isolated and seeded on Matrigel and non-Matrigel coated tissue culture flasks in growth medium containing 0 ng/mL, 2.5 ng/mL, 5 ng/mL or 10 ng/mL basic fibroblast growth factor (bFGF). After passaging the cells four times cell counts were taken and the cells were grown in differentiation medium in PDMS molds to create muscle bundles. Cell counts showed that the greatest number of cells occurred in the population grown on Matrigel in a growth medium containing 5 ng/mL. After two weeks the muscle bundle functionality was tested by their force output. The population grown in 10 ng/mL of bFGF produced the greatest force even with low cell counts. The bundles were then stained in order to characterize the cell types present in each of the populations. The population grown in 2.5 ng/mL bFGF showed the greatest number of cells, but the population grown in 10 ng/mL bFGF showed a purer population with a larger ratio of myoblasts to fibroblasts. In summary, this study shows that bFGF and Matrigel are necessary for creating an optimal growth environment to grow skeletal muscle derived cells. Also, increasing the concentration of bFGF creates a purer population of cells by limiting the growth of fibroblasts in culture. REU Fellow: Alice Welsh, Biomedical Engineering Major, Senior, North Carolina State University Quantifying Gap Junctional Coupling between Cardiomyocytes and Other Cell Types Mentors: Dr. Nenad Bursac, Assistant Professor, and Luke McSpadden, Graduate Student, Biomedical Engineering Alice Welsh is a senior biomedical engineering major at North Carolina State University. The purpose of her project was to determine gap junctional coupling between cardiomyocytes and other cells types. Cardiac cells are connected to each other by channels called gap junctions; these channels allow ions and small molecules to pass between adjacent cells. The presence of these junctions allows for electrical signals within the heart to propagate from cell to cell, causing the contraction of the heart which pumps blood throughout the body. The formation of gap junctions between other cell types and cardiomyocytes results in slowed conduction of the action potentials of the heart, leading to unpredictable signal propagation. It was hypothesized that gap junctions would only form between cardiomyocytes and other cells that contain connexins, which are important gap junctional proteins. In order to quantify the gap junctional coupling between cardiomyocytes and other loading cells, a technique involving dye transfer followed by fluorescent-activated cell sorting (FACS) analysis was implemented. Donor cells were stained with two dyes: one small enough to move through gap junctions, calcein AM, and one that was too large, DiI. The percentage of cells which uptake the calcein but not DiI can be used as a measure of gap junctional coupling between the cell types. The appropriate dye concentration and absorption times were determined, as was the most effective staining procedure and donor to recipient ratio. The initial results were good but the theory that yielded promising results with human embryonic kidney (HEK) cells did not hold up for cardiomyocyte donor cells. This study helped clarify what process would not work for cardiomyocytes, and gives some direction for procedures and approaches in future studies. procedures. This project let Alice know for sure that she wishes to continue research in biomedical engineering and she is currently applying to graduate programs, including Duke. REU Fellow: Kassandra Thomson, Biomedical Engineering, University of Texas at Austin The Visualization and Quantification of Collagen Deposition by Cardiac Cell Cultures Kassandra Thomson is a biomedical engineering major from the University of Texas at Austen. Cardiac fibrosis is a major component of heart disease, and can lead to heart failure as the cardiac muscle stiffens. It is important to build models of diseased heart tissue in order to study the effects of fibrosis on the electrical properties of cardiac cells. The aim of this study was to develop a method to visualize and quantify collagen deposition by 2D cardiac cell cultures in vitro to determine if collagen was being deposited between cardiomyocytes, thus interrupting electrical propagation. Collagen deposition was also compared between samples of different age, with different concentrations of ascorbic acid, and isotropic versus anisotropic. Immunostaining was the primary method of visualization used. A new method was developed to stain extracellular collagen separately from intracellular collagen. A hydroxyproline assay was tried in order to quantify the amount of collagen present in cell cultures. Extracellular collagen staining was achieved in cardiac fibroblast cultures, but not with cardiomyocytes. For fibroblasts, there is a visible increase in the amount of collagen deposition with cultures of increasing age and with increasing amounts of ascorbic acid. Changes in collagen deposition with cellular patterning have not yet been determined. The hydroxyproline assay is currently being formatted to our cell cultures, and has not yet worked successfully. Project #14: Programming A New Type of Multicore Processor Advisor:Dan Sorin, Electrical and Computer Engineering Prof. Sorin's research group has developed a new type of multicore processor that includes general purpose cores (CPUs) and graphics processing units (GPUs). The novelty of the new system is in how the CPUs and GPUs communicate with each other, and this new communication is vastly more efficient than previous schemes. To take advantage of this faster communication, we need to re-write programs that were written in CUDA or OpenCL. The potential for performance improvement is very large (10-100x speedups), and we seek students who can learn new programming skills and incorporate knowledge of the hardware to write better software. Najae Prelow, Junior, Computer Engineering Major, Jackson State University Mentors: Dr. Dan Sorin, Electrical and Computer Engineering and Blake Hechtman, graduate student Project Title: Managing Parallelism and Synchronization in the GPU The GPU (graphics processing unit) is a high performance chip. They are comprised of thousands of tiny efficient cores that are mainly used to accelerate the creation of graphics. GPUs are commonly used in electronic devices such as gaming systems, computers, and many other devices that uses graphics. GPUs are great for not only accelerating the creation of graphics, but also for parallel algorithms. The reason why GPUs are great for parallel algorithms is because they can spread out over the thousands the cores of the GPU and occupy all the space. Non-parallel algorithms on the other hand are not compatible to run on the GPU. GPUs are designed for parallel computations which makes it immense in high efficiency resources. With this in mind the idea to take advantage of the efficiency was hatched. In order to tap into the GPU’s high power we had to utilize several different methods. First we rearranged the code according to what the computer does well. In this case we used an OpenCl based runtime which was developed by a PHD student this summer at Duke University. Next we rewrote the algorithms in Cynk. Cynk was also created by a graduate student here at Duke University. Cynk is a new programming language that he developed which is based on an OpenCl runtime. Due to the OpenCl runtime which efficiently and effectively supports task-based parallelism, we are able to to make the algorithm task parallel. This process essentially optimizes the speed and the power of the way algorithms are processed. Bryan Anthonio, Sophomore, Engineering Physics, Cornell University Mentor: Dr. Dan Sorin, Associate Professor, Department of Electrical and Computer Engineering and Ralph Nathan, PhD Candidate, Department of Electrical and Computer Engineering Project Title: Recycled Error Bits: Architectural Support for Energy-Efficient and Numerically Accurate Software In numerical software, double precision is often preferred over single precision for concerns relating to the smaller amount of numerical accuracy offered by single precision. Rounding error often constrains the accuracy of numerical software due to the finite precision of FPUs, making the use of double precision more prominent. However, the use of double precision often leads to significant energy costs, as it can be more burdensome to hardware due to the increased transfer of data to and from memory. The purpose of this investigation is to facilitate the development of numerical software that is both accurate and energy efficient. We demonstrate that “recycling” the rounding error of each floating-point operation and allowing it to be utilized, if desired, can achieve this. Our experiments show that by doing this, numerical software can either achieve greater accuracy with comparable performance and energy use or comparable accuracy with greater performance and less energy use. Project #15: Design and Evaluation of a Computer Processor that Tolerates Faults Advisor:Dan Sorin, Electrical and Computer Engineering Prof. Sorin's research group is developing the first low-cost multicore processor that can tolerate faults as it runs, without the user ever knowing that any problems had occurred. There are many challenges to be solved, including how to detect when certain errors occur and how to demonstrate that the chip design actually achieves its goals at reasonable power and chip area costs. We seek students who want to "get their hands dirty" in hardware design and experimentation Project #16: Thickness Variation in Polymer Thin Films Deposited by Resonant Infrared Matrix-Assisted Pulsed Laser Evaporation Advisor: Adrienne Stiff-Roberts, Associate Professor, Electrical and Computer Engineering Resonant infrared matrix-assisted pulsed laser evaporation (RIR-MAPLE) is a promising deposition technology for the fabrication of conjugated polymer-based optoelectronic devices for two primary reasons: i) the ability to control film morphology, and ii) the ability to deposit multi-layered heterostructures. The Stiff-Roberts group has developed a variation of RIR-MAPLE that uses emulsified targets of organic solvents and water such that the incident laser wavelength (Er:YAG at 2.9 µm) is resonant with hydroxyl (O-H) bonds in the host matrix, which are absent from the guest material. The novelty of the approach lies in the fact that while most polymers of interest and many compatible solvents do not resonantly absorb the laser energy at 2.9 μm, the emulsion with water enables high-quality, thin-film deposition with minimal photochemical and structural degradation for almost any polymer of interest. In order to fabricate polymer-based optoelectronic device heterostructures, careful control over film thickness across a substrate is required. In this project, atomic force microscopy (AFM) will be used to characterize film thickness of polymer thin films across an entire substrate as a function of RIR-MAPLE growth parameters. The goals is to determine the thickness uniformity of the thin films for application to optoelectronic devices. Project #17: Heterogeneous Datacenter Design and Deployment Advisor: Benjamin Lee, Assistant Professor, Electrical and Computer Engineering Demand for computing capacity is driven by the data deluge. Over the past 45 years, computer engine,ers have transformed exponentially increasing transistor density into exponentially increasing capacity. At present, energy costs jeopardize further scaling. The US Environmental Protection Agency estimates datacenters already consume 1.5% of total nationwide electricity, which is comparable to the consumption of 5.8M US households. No combination of existing datacenter architectures can improve computing capacity by the desired three orders of magnitude within datacenter power budgets, which are already at megawatt scales. This project examines the design and deployment of heterogeneous datacenter architectures that improve efficiency by 10x. Heterogeneity deploys a mix of specialized hardware for a mix of software needs, improving efficiency as unnecessary hardware resources are eliminated. To build heterogeneous datacenters, we explore design spaces for processors, memory, network, and storage using techniques in statistical inference and machine learning. To deploy heterogeneous datacenters, we use multi-agent markets in which applications bid for heterogeneous architectures, maximizing utility. REU students participating in this project may participate in data collection and analysis. Responsibilities may include (1) analyzing performance and power for a variety of processor and memory designs, (2) simulating future processor and memory designs, (3) performing data analysis and design optimization. While not required, some knowledge in computer architecture and a major programming language (e.g., C, C++, Java) is helpful. Project #18: RF and Antenna Design for Communication and Imaging Advisor: Qing H. Liu, Professor of Electrical & Computer Engineering The objective of this project is to design and fabricate small antennas for communication and imaging applications. The student will utlize computer software to design antennas, build antennas in the laboratory, and perform communication and imaging measurements. Ugonna Ohiri, Computer Engineering Major, University of Maryland- Baltimore County Ultra Wideband Antennas Mentors: Dr. Qing Liu, Professor, Department of Electrical and Computer Engineering and Luis Tobon Llano, Graduate Student, Department of Electrical and Computer Engineering Ugonna Ohiri is a computer engineering major from the University of Maryland-Baltimore County. His research focused on antennas with both multiple frequencies of resonance and widebroadband performance which have played a major role in the functionalities of wireless communication systems. In his project, he used the Sierpinski Carpet Mod-P fractal antenna based on fractal geometry. In our experiment, we constructed three iterations using both software simulations and experimental validation as measurements to test various parameters. The effect of further fractal iterations on the overall efficiency of the antenna is studied. Both the simulations and experiments show consistent results when weighed against each other. Overall, the results show the third iteration as being the most efficient iteration, when compared to the preceding three. Wesley D. Sims, Physics Major, Morehouse College Using Microwave Imaging for Breast Cancer Detection Wesley Sims is a senior physics major from Morehouse College. Microwave imaging for breast cancer detection is based on the contrast in electrical properties of healthy breast tissues and malignant tumors. My project contributed to the research of breast cancer detection using microwave imaging as an REU Fellow at the Pratt School of Engineering at Duke University. The purpose of this project is to assist in the ability to detect breast cancer by using microwave imaging. Microwave imaging is a much healthier methods for breast cancer detection than current methods in use. I assisted in the proposed design of a clinical system to be used at Duke University to do testing through multiple clinical trials. I helped to design the bed-like structure with an integrated chamber that will collect images of a patients’ breast tissue. In addition, I helped to design and simulate major components of the proposed switching system. Part of my research involved making schematic drawings of a proposed clinical system and a single pad of a circuit board layout. I also performed tests and obtained results from simulations done in Agilent Automated Design System to be used in refining the system for future use. Jack Skinner is an electrical engineering major from Ohio Northern University. Microwave Imaging (MWI) is an emerging technique for the detection of breast cancer and other biomedical anomalies. The success of microwave imaging is due to the distinct differences in electrical properties between malignant tumors and healthy mammary tissue. This new imaging technique uses non-ionizing radiation to produce a full 3-D image of the anomaly based on scattered microwave energy. This paper focuses on the research and construction of an experimental 3-D MWI system, as well as some of the theory behind microwave imaging. The MWI system will use a 3-D array of folded patch antennas to send and receive an RF signal. The transmitted signal will be scattered by an object (tumor) and then recorded by various antenna combinations. These measurements, known as S21 parameters, will be used in an inversion algorithm to reconstruct the inverted dielectric constant and conductivity of the medium and the target itself. This research discusses the major components of the MWI system: the antenna array, imaging chamber, switching system, network analyzer, and PC used to run LabVIEW software and record the data. The conclusion of Jack’s research has resulted in a functional 3-D MWI system, with only issues of the switching system and matching fluid to be resolved before a series of tests will be run to reconstruct sample images. In addition, another new imaging technique, microwave-induced thermoacoustic imaging (MITI), was discussed and reviewed. This imaging technique will use short pulsed, high power microwave energy to irradiate the mammary tissue and possible tumors. The tissue and tumor will then heat up and expand, causing a variation in fluid pressure. The difference in pressure will induce an acoustic signal that will be recorded by an ultrasonic transducer and amplified. The amplified signal will be converted to a digital signal to be used in image reconstruction. Project #19: Design-for-Testability Methods for Multicore Integrated Circuits Advisor: Krishnendu Chakrabarty, Professor Electrical and Computer Engineering Multicore integrated circuits (or “muticore chips”) are being used today in microprocessors to achieve high performance under power constraints. Processor chips with four cores from companies such as Intel and AMD are now common, and up to 16 cores are going to become mainstream quite soon. These multicore chips are giving us unprecedented computing power for scientific applications, gaming and entertainment, control systems, and business software. For graphics applications and graphics processors (GPUs) from companies such as Nvidia, many more cores are integrated in a single chip. This project is focused on cutting-edge design-for-testability (DFT) techniques for multicore chips. We are developing DFT solutions that can reduce manufacturing cost and make these chips more dependable for user applications. Our research involves collaboration with Intel and AMD. Desired skillset: A first course in logic design and computer hardware, basic knowledge of electronic circuits, some understanding of computer architecture/organization, programming in C/C++. Project #20: Optimization Methods, Chip Design, and Software Development for Digital Microfluidic Biochips Advisor: Krishnendu Chakrabarty, Professor Electrical and Computer Engineering Advances in digital microfluidics have led to the promise of biochips for applications such as point-of-care medical diagnostics. These devices enable the precise control of nanoliter droplets of biochemical samples and reagents. Therefore, integrated circuit (IC) technology can be used to transport and process “biochemical payload” in the form of nanoliter/picoliter droplets. As a result, non-traditional biomedical applications and markets are opening up fundamentally new uses for ICs. In this interdisciplinary research project, we are studying ways to design biochips that can produce accurate results for clinical diagnostics in the shortest possible time and with minimum chip area. We are collaborating with other faculty and a start-up company in Research Triangle Park. Desired skillset: A first course in logic design and computer hardware, high-school or freshmen Chemistry lab work, programming in C/C++, basic knowledge of optimization and computer algorithms. Project # 21 (WISeNet): Dynamic Optimization of Enterprise Systems Using Real-Time Sensor Measurements and Adaptive Feedback Control Advisor: Dr. Krishnendu Chakrabarty, Professor, Electrical and Computer Engineering and Dr. Silvia Ferrari, Professor, Mechanical Engineering and Materials Science (WISeNet) The goal of adaptive feedback control for enterprise systems (ES) is to develop data-centric techniques for designing an adaptive ES to enable the highest level of agility, performance, and efficiency. Adaptive model reference and reinforcement learning techniques will provide the foundation for a smart software mediation layer that enables the ES to be self-learning, adaptive to dynamic/diverse service requests and resource availability, based on real-time sensor measurements from ES nodes, as well as support a network of service providers and users within a complex information ecosystem. The focus of this project is integrate, for the first time, policy management and production planning with data-driven adaptive control to realize a dynamic information ecosystem. Our vision is a smart enterprise-wide system that automatically adapts to emerging system behaviors by dynamically evolving optimization strategies in real-time and without disruption. This level of adaptation, seamless efficiency, uninterrupted service from the perspectives of users and providers, is a significant step forward towards smart enterprise systems. To date, most adaptive control methods, including MRAC, are applicable to linear or, in some cases, nonlinear dynamical systems that can be modeled by an ordinary differential equation or transfer function derived from first principles. This research will develop an adaptive control method for influence diagram (ID) models of enterprise systems that can be learned from data, and that can take into account uncertainties and errors inherent to all ES and their users. Professor Chakrabarty’s research is focused on testing and design-for-testability of integrated circuits; digital microfluidics, biochips, and cyberphysical systems; optimization of digital print and production system infrastructure. His research projects in the recent past have also included chip cooling using digital microfluidics, wireless sensor networks, and real-time embedded systems. The goal of the REU fellow will be to develop and influence diagram model of an enterprise systems using learning algorithms and simulation data from an existing virtual printing factory. Project #22 (WISeNet): Drought Monitoring and Prediction in Semiarid Climates Advisor: Dr. John Albertson, Professor, Civil and Environmental Engineering (WISeNet) A secure supply of drinking water is a fundamental human need that goes unmet for much of the world’s population. Although water quality can be ensured through engineered treatment and delivery facilities, the quantity of future water availability remains surrounded by significant scientific uncertainty. This project will utilize data and simulations developed using a long-standing NSF-funded broad network of soil moisture sensors and lower atmosphere sensors on the island of Sardinia that are designed to address an important knowledge gap, i.e., how changes in the seasonality of precipitation in semi-arid regions interact with vegetation dynamics to affect available surface-water resources. Developing mathematical models that capture not only the dynamics of the environmental and ecological system, but also its interactions with the wireless sensors, is critical both to sensor management and data processing algorithms. A fundamental challenge in environmental sensing and prediction is accounting for the coupling between the sensor performance and the local environment, which greatly influences the sensor’s visibility region and communication signal. This research project aims to develop interdisciplinary models of global environmental dynamics coupled with spatiotemporal models of sensor measurements for the environmental process of their choice. The goal of the REU fellow will be to develop probabilistic sensor models that capture the most significant relationships between local environmental conditions and the sensor’s measurements, mode, and communication signal. Using available optimization algorithms, the fellow will then use the sensor models to obtain optimal sensor deployments for the design of the field site, and repopulation by means of new and possibly mobile sensors. Malini Nambiar, Junior, Earth and Environmental Engineering, Columbia University, School of Engineering and Applied Sciences Mentor: Dr. John D. Albertson Project Title: “Contrasting Competing Forest Management Practices in Water-Limited Ecosystems” It has been well-established that vegetational land cover has a direct impact on atmospheric fluxes in mass, momentum, and energy, which in turn influence climate dynamics. Temporal structure analysis can be used to characterize hydrological interactions between various vegetational types and the atmospheric boundary layer. This study utilizes computational analysis to determine basic differences in surface hydrological fluxes and water recharge in the southeastern United States, given pine and eucalyptus vegetation models. A basic one-dimensional “bucket model” (as described in Guswa, 2002) was adopted as the basis for computation of total water flux, using loblolly pine (Pinus taeda) data from the Blackwood Division of the Duke Forest. Preliminary data analyses show that overall evapotranspiration rates are lower for eucalyptus than pine, given computed soil moisture, potentially resulting in lower water availability and ecosystem water stress. Project #23 (WISeNet): Aforestation, Climate Change Mitigation and Prediction Advisors: Dr. John Albertson and Gabriel Katul, Professors, Civil and Environmental Engineering / Nicholas School of the Environment (WISeNet) Distributed sensing is crucial to understanding environmental change, and to protecting the health of humans. Federal agencies are already in a planning phase for their integration with national research platforms such as NEON and CLEANER. Dr. Albertson’s and Dr. Katul’s research addresses a primary question in climate change pertaining to the mediating role of the biosphere on elevated atmospheric CO2 concentration, and their influence on rainfall and mean air temperature. The ability of terrestrial ecosystems to absorb CO2 is sensitive to atmospheric conditions, and is characterized by feedback loops that, if characterized by intensive sensor data, can lead to far more accurate predictions. This research project gives students the unique opportunity to employ a wide array of wireless sensors, e.g. gas analyzers, anemometers, and sap flux sensors, presently deployed in the Duke Forest, to collect measurements of precipitation, soil moisture, vapor pressure deficit, temperature, and, more importantly, photosynthetically active radiation. The REU fellow will use simulation and data processing algorithms to develop improved models that capture the rich spatial variability in ecosystem carbon dynamics, and natural feedback loops from the environmental controls to surface radiative, physiological, and aerodynamic process, to predict their effects on warming potential. Dominique Williams, Junior, Civil Engineering, Jackson State University Mentor: Dr. John Albertson, Professor and Chair, Department of Civil Engineering Project Title: The North Atlantic Oscillation The North Atlantic Oscillation is a prevailing mode of atmospheric variability that rest and remans in the Atlantic Ocean. It is the oldest and most famous pattern of variability. This distinct weather pattern has been researched for more than 100 years by excellent scholars, professors, scientist, and meteorologist. It most commonly affects the southwestern Europe and the eastern United States. It affects these two regions more commonly just because the Atlantic ocean is centered between the two. The NAO undergoes two phases the positive phase and the negative phase. Since the eastern United States and the southwestern Europe are most commonly affected by the NOA they experience these phases. As an example southwestern Europe could experience hot and dry winters during the positive phase. During the negative phase southwestern Europe would experience cold and wet winters. This is not particular good for there water systems. In reference to the eastern United States this means a significant increase in precipitation, a significant increase in snow occurrence in the northern area, and an increase in moisture convergence. During my time at Duke University my main goal has been to compare runoff vs. Growth (Runoff of precipitation). I have been mainly looking into the spring season but specifically at the winter season. During the spring season this is when we see runoff which is common after winter. With the data that past researchers have found, it has been my job to look for a recurrent change in precipitation patterns. I have been looking into all months individually and in groups to get an ideal visualization. With the data that I had been given, I had been using a mathematically based program to compute statistics and standard deviations. So far not much recurrent patterns has been seen but there may be others solutions. Project #24: Multi-scale Multi-mechanism Design of Tough and Bioactive Hydrogels Advisor: Xuanhe Zhao, Assistant Professor, Mechanical Engineering and Materials Science, and Soft Active Materials Laboratory Human tissues need to be mechanically robust in order to carry substantial internal and external forces over time. For instance, articular cartilage is a natural hydrogel that contains 70% water but can maintain impressively high fracture toughness (i.e., >1000 Jm-2) over millions of cycles of loads equivalent to body weights. On the other hand, most synthetic hydrogels are brittle with toughness less than 100 Jm-2. To date, the replacements for injured or diseased load-bearing tissues such as cartilages and spine disks still rely on metals and rigid polymers, sacrificing bioactivity and flexibility for mechanical robustness. Development of tough and bioactive hydrogels as artificial tissues will have huge impacts on both millions of peoples’ wellbeing and a multi-billion-dollar biomaterial industry, addressing critical healthcare challenges posed by our aging society. Inspired by the mechanics and structures of tough biological tissues, we propose that a general principle for the design of tough hydrogels is to implement mechanisms for dissipating mechanical energy and maintaining high elasticity into hydrogels. A particularly promising strategy for the design is to integrate multiple pairs of mechanisms across multiple length scales into a hydrogel. Guided by the design principle and strategy, we develop a new hydrogel system with extremely high toughness (> 9000 Jm-2) as well as capability of stem-cell encapsulation for tissue regeneration. Applications of the tough and bioactive hydrogels are being explored, in particular, by 3D printing them into various prototypes. Xuanhe Zhao is Assistant Professor of Mechanical Engineering and Materials Science at Duke University. He received his PhD in Mechanical Engineering from Harvard University in 2009, MS in Materials Engineering from University of British Columbia in 2006, and BE in Electrical Engineering from Tianjin University in 2003. Dr. Zhao's current research is focused on understanding the fundamental mechanics and physics of materials and phenomena emerging on the interface between engineering and biological systems and to design new materials and structures capable of extraordinary functions (http://www. zhaogroup.org). Dr. Zhao is a recipient of the NSF CAREER Award and the Early Career Researchers Award from AVS Biomaterial Interfaces Division. Project #25: Targeted drug delivery to single cells by cavitation bubbles Advisor: Pei Zhong, Professor, Mechanical Engineering and Materials Science We have developed a unique microfluidics-based system for investigating cavitation bubble(s)-cell interaction with potential applications in targeted drug delivery and mechanical stimulation of individual cells. The REU Fellow will have the opportunity to participate in this exciting new project, specifically in conducting high-speed imaging experiments to correlate bubble and associated fluid dynamics with resultant membrane permeabilization and macromolecular uptake in the target cells assessed by optical and fluorescent microscopy.The REU Fellow may also be involved in additional work in microfluidic device design, fabrication and integration with an ultrasound applicator. A solid engineering background in MEMS and BME, and strong motivation and dedication for scientific research are required.Appropriate technical training will be provided to the student at the beginning of the project. Emily Schapker, Senior, Mechanical Engineering, University of Kansas Mentors: Dr. Pei Zhong, Professor, Duke University and Fang Yuan, PhD Candidate, Duke University Project Title: Tandem Microbubbles for Single Cell Manipulation Microbubble collapse and the resulting jets have been used in a variety of biological applications, such as shockwave lithotripsy. The use of bubble jets for cellular manipulation offers great promise for drug delivery and cell differentiation. Recent studies in tandem bubble dynamics have shown that laser-induced cavitations can produce jets of controlled speed in a microfluidic chip for cell deformation and poration. In order to ensure that pores can be formed without resulting in cell death, it is necessary to determine the maximum strain that a cells can withstand during jet interaction. It is also necessary to understand the parameters that may affect cell strain, such as media viscosity and the shape of the adhesion pattern between the cell and the substrate. To investigate this, cells were seated in a microfluidic chip and 3μm polystyrene beads were attached to the cell surface. The chip was fabricated to include two gold dots for laser-induced bubble generation, along with a substrate pattern in “H” and “I” shapes. Experiments were conducted in a control solution of culture media as well as a Ficoll solutions was prepared to increase the media viscosity to approximately that of blood. Jets with speeds of approximately 50 m/s were generated in the chip 20 μm away from the cell. Deformation was recorded using a high-speed camera and displacement of the markers was tracked using Matlab code. These discrete points were then used to calculate the maximum strain and shear stress on the cell. Analysis of the markers showed that maximum displacement was 2.4 times greater for “I” adhesion patterns. It was also observed that average maximum shear stress on the cell was 3.7 times higher for the 0% Ficoll solution over the 8% Ficoll solution. While these results provide valuable information for understanding the parameters that impact cell poration, the study only allowed for a limited collection of data points. In order to increase the statistical significance of the findings, it is recommended that more data points be collected, in addition to revising the algorithm of the code to improve accuracy. It is also suggested that data be collected for cell viability following poration, to compare the maximum principal strains with the occurance of cell death. Project # 26: Cooperative active sensing for networks of mobile robots Advisor: Michael Zavlanos, Assistant Professor, Mechanical Engineering and Materials Science and Electrical and Computer Engineering Controlling teams of small, inexpensive and agile autonomous robots has recently become a very promising approach towards the design of more modular and robust robotic systems. The focus of this research is on networks of small, ground and aerial, mobile robots carrying specialized, inexpensive and possibly inaccurate sensors. These systems can be used for a wide range of tasks including environmental monitoring and mapping, cooperative manipulation, and search and rescue missions. While such tasks have been tested with great success in controlled lab environments, the sensing and coordination mechanisms needed for precise localization, ego-motion estimation, and control in uncertain and unpredictable environments remain underdeveloped. To conceptualize the proposed research, consider a team of mobile robots in, e.g., a target tracking mission, with the objective to precisely localize a group of moving targets, report their data to a certain location, and respond to the situation. Robots that can sense the targets make noisy measurements of their locations. In this project we focus on stereo vision sensors as they are lightweight, inexpensive, and provide both depth and bearing measurements of a target from a single pair of simultaneous images. Differentiation of these stereo measurements provides an estimate for the uncertainty of the target's location. On the other hand, the asymmetric nature of stereo vision, e.g., field-of-view constraints, requires that robots observe subsets of targets at a time. This necessitates protocols to assign targets and roles to different robots. The necessary coordination between robots and decomposition of roles can result in significant improvements in localization, area coverage, and utilization of resources. For this, the robots need to communicate and share their measurements of the target locations, the subsets of targets that they are responsible for observing, and their particular roles within the team. Communication occurs via dedicated wireless channels between pairs of robots that are in range. The communication variables that need to be determined and controlled are routes and rates that allow reliable information exchange in the network. To improve on the localization accuracy of the targets, any new measurements that are made and communicated by the robots are fused with prior history using a Kalman filter. In the absence of a central location that collects and fuses all information from the sensors, these measurements are fused in a distributed way. The goal of this project is to integrate mobility, specialization, and collaborative sensing in a distributed multi-robot system that allows for reliable and on-demand sensing accuracy as the task, e.g., the mobile target, evolves in space and time. The Zavlanos Laboratory specializes in the area of networked dynamical systems and distributed control, with applications to robotic, sensor, and communication networks. The interested REU fellow will get involved with the development of algorithms and/or their experimental validation. They will obtain experience in controls, robotics, sensing, and/or communications, as well as in the mathematical and computational techniques required for the study of such systems. Students with a background in Mechanical Engineering, Electrical Engineering, or Computer Science, are encouraged to apply. Project #27 (WISeNet): Decentralized Sensor Guidance and Control in Complex ObstaclePopulated Environments Advisors: Dr. Michael Zavlanos, Assistant Professor, , Mechanical Engineering and Materials Science, and Dr. Silvia Ferrari, Professor, Mechanical Engineering and Materials Science (WISeNet) Methods for vehicle guidance (or motion planning) and control typically are designed to compute a vehicle’s trajectory between two or more waypoints subject to navigation objectives, such as collision avoidance and minimum-fuel consumption. Mobile sensors consist of sensor-equipped vehicles that are deployed primarily to perform target detection, classification, surveillance, and/or tracking. Thus, they require the sensor’s field-of-view (FOV), or visibility region, to intersect the target geometry in order to obtain measurements from the target. Since the FOV typically is bounded, the sensor’s position and orientation determine what targets can be measured at any given time. Thus, the vehicle’s trajectory must be planned in concert with the sensor’s measurement sequence. Finding optimal vehicle trajectories is intractable even under simple constraints. This problem is aggravated by the fact that many modern sensors are deployed as a part of a network that is possibly heterogeneous, and must account for communication constraints, to allow sensors to communicate with each other and/or a base (central) station. The Zavlanos Laboratory specializes in the area of networked dynamical systems and distributed control, with applications to robotic, sensor, biomolecular, and social networks. The goal of the REU fellow will develop new guidance methods for mobile sensor networks by investigating how approaches such as optimal control, potential field, and probabilistic roadmap methods can be modified to account for the expected information value of the targets, based on the local environmental conditions. Project # 28 (WISeNet): Biologically-inspired Intelligent Sensor Networks Advisor: Dr. Silvia Ferrari, Professor, Mechanical Engineering and Materials Science and Dr. John Alberston, Professor, Civil and Environmental Engineering (WISeNet) Intelligent sensor networks consist of multiple heterogeneous vehicles, such as ground, air, and underwater robots, each equipped with heterogeneous sensing and wireless communication devices that work together toward a common objective. By cooperating and exploiting their complementarities, these networks can exhibit enhanced sensing performance and navigation in complex environments through the use of sensor fusion and data-sharing algorithms. As a result, heterogeneous sensor networks are now being increasingly utilized to remove humans from monitoring and surveillance tasks that are hazardous, tedious, or must last over long periods of time. Some of the applications we will consider in this project include alpine search-and-rescue; robotic serpentine monitoring to detect leaks of greenhouse emissions from covered landfills or from CO2 sequestration fields; environmental monitoring of air quality near major highways; monitoring of physical variables in agricultural and greenhouse environments; and monitoring of oil leaks in refineries for Leak Detection and Repair (LDAR). In all of these applications, the robotic sensors must carry out multiple complex tasks, such as, cover a region of interest, detect, track, classify, and possibly pursue multiple targets, while simultaneously avoiding obstacles and maintaining connectivity with a base station. Dr. Ferrari’s Laboratory for Intelligent Systems and Control (LISC), develops guidance and control methods for mobile sensor networks, using interdisciplinary methods inspired by biological systems, statistics, and computer science. As part of this project, the REU fellow will help develop and test a hierarchical command and control software architecture for the coordination and control of sensor networks, which will be comprised of three modular components for mission planning, trajectory planning, and vehicle control. Project: #29: Construction of an atomic force microscope for combined mechanical and optical measurements Advisor: Piotr Marszalek, Professor, Mechanical Engineering and Materials Science The objective of this project is to provide hands-on experience to undergraduate students in the design and construction of a robust high-precision and research-grade atomic force microscope that can be operated on top of an inverted optical microscope for combined force and fluorescence measurements. We note that a complete home-made AFM instrument was already designed, constructed and successfully used in the Marszalek laboratory by several undergraduates and its design was published by Rabbi and Marszalek (Mr. Rabbi was a Duke ME undergraduate student). This AFM instrument will require a complete design overhaul to be able to work on top of an inverted microscope. (Some details of this overhall follow, and below that in italics, is the impact and value of this project): To capture fluorescence from the molecule being stretched by the AFM, the microscope objective needs to be inserted into the AFM head and positioned right below the sample. It will occupy the space that in a traditional AFM is taken by a high precision piezoelectric stage that translated the sample in the z direction for the mechanical stretching of molecules. Therefore, in the new AFM, the Z-stage that moves the sample will need to be located outside of the AFM head. One of the main difficulties for the new AFM to operate successfully will be to keep the molecule stretched within the focal depth of the microscope objective. To achieve this goal, the whole AFM head will need to be also translated in the Z direction, relative to the sample. This can be achieved by attaching another high precision piezoelectric Z stage directly to the top of the AFM head and mounting it on the body of the optical microscope. This modification will force the relocation of the laser from the top of the head to a horizontal location inside the head. ) This project will involve undergraduate students who will work over the summer in Dr. Marszalek’s laboratory to design and construct such an instrument. This project will provide an extremely fulfilling experience for these undergraduate students in the planning and execution of their real-world engineering activities whose final product will be a sophisticated research-grade instrument. The students will directly get experience in designing and constructing an instrument which is composed of very precise mechanical, electrical, electronic, and opto-elecronic components, which need to be perfectly aligned and actuated/probed by digital to analog interfaces controlled by a computer. Thus, their practical experience will integrate many areas of engineering. Importantly their product will be later used for real research activities done by their undergraduate peers. These activities will focus on simultaneous measurements of the elastic and optical properties of single molecules such as DNA and various proteins (force spectroscopy) that will be labeled with fluorescent probes. Project: #30: Mechanical Folding of Individual Polypeptide Chains by AFM Advisor: Piotr Marszalek, Professor, Mechanical Engineering and Materials Science The folding of proteins is one of the most important yet not completely understood topics in biology. The question “Can we predict how proteins will fold?” was listed in 2005 as one of the 125 most important unsolved problems in science by the Science magazine. Significant progress has been made toward understanding the protein folding through in vitro experiments and computer simulations, but much less is known about folding in vivo. During co-translational folding, the nascent polypeptide chain (NPC) is extruded sequentially in a vectorial manner from the ribosome exit tunnel and starts folding under severe conformational constraints. It is presently unknown how such 1D constraints affect the folding pathway. The long-term objective of this proposal is to advance understanding of protein folding by: a) studying the vectorial folding of single proteins under 1D constraints by Atomic Force Microscopy(AFM)-based single-molecule force spectroscopy (AFM-SMFS) and computer simulations using steered molecular dynamics (SMD) calculations. b) directly examining the folding behavior of the nascent polypeptide chain emerging from the ribosome using AFM imaging and mechanical manipulations (Fig. 1). Atomic force microscopy is a novel form of (non-optical) microscopy that can be mastered easily by undergraduate students. Although some knowledge of biology as it relates to proteins and their “folding” problem would be desirable it is not a pre-requisite for participation Project #31 : Investigating DNA Mismatch Repair Through Single-Molecule Approaches Advisor: Piotr Marszalek, Professor, Mechanical Engineering and Materials Science Even though tremendous progress has been made in elucidating DNA mismatch repair, mainly through biochemical studies, many critically important details of DNA repair mechanisms remain obscure and controversial, even for E. coli’s MMR system, which is the simplest and best characterized. This is because MMR involves an orchestrated activity of many proteins such as MutS, MutL and MutH, which form transient complexes between themselves and with DNA that are difficult to monitor in real time. The main goal of the current proposal is to unravel the mechanism of E. coli mismatch repair through the application of a suite of single-molecule techniques, such as AFM, Optical Tweezers (OT) and single-molecule fluorescence resonance energy transfer (SM-FRET). Specifically, AFM imaging and volumetric measurements will be used to examine the structure of MutS tetramers and MutS complexes with MutL to determine the oligomeric status of both proteins in complexes with heteroduplex (mismatch carrying) DNA in the absence and presence of ATP/ADP. AFM force spectroscopy will be used to measure, mechanically the interactions within MutS dimers as well as the effect of adenine nucleotides on these interactions, while optical tweezers will be used to measure similar interactions within MutS tetramers as well as between MutS tetramers and DNA. MutS-controlled DNA looping mechanisms and pathways will be thoroughly examined using Optical Tweezers. SM-FRET will be used to follow, in real time, the position of the MMR proteins relative to key DNA sites (the mismatch site and strand signal site) and the distance and contact between these key DNA sites will be probed during the MMR reaction by all three techniques through mechanical and optical (fluorescence) detection. These singlemolecule approaches will verify a new MMR signaling model, in which the mismatch site and the site of DNA incision are brought to contact by the concerted work of two MutS dimers through a DNA looping-sliding mechanism. These approaches promise to unravel the details of the MMR mechanism that so far have proved very difficult to elucidate by traditional methods. The new results will significantly expand the knowledge base about one of the key mechanisms that is responsible for the maintenance of genomic stability and will lay the groundwork for future studies of eukaryotic MMR. Methodologies developed for this model system may prove useful for studying other DNA repair systems and more generally to investigate protein-protein and DNA–protein interactions. Project # 32: Self-Cleaning Materials Advisor: Chuan-Hua Chen, Assistant Professor, Department of Mechanical Engineering and Materials Science The objective of this project is to create self-cleaning materials that function regardless of external forces, including gravity. The project takes advantage of the jumping-drop discovery at Duke, where water condensate self-propels to jump away from superhydrophobic surfaces, carrying away contaminants in the condensate drop. The background is discussed in the magazine Scientific American (https://web.duke.edu/uphyl/Scientific_American.pdf). This project is primarily experimental but will also involve the development of scaling laws. The student will have the opportunity to use high-speed photography to the self-cleaning process at up to a million frames per second, and use the mechanistic understanding to guide the engineering of practical self-cleaning materials. Project # 33: Surface Energy Harvesting Advisor: Chuan-Hua Chen, Assistant Professor, Department of Mechanical Engineering and Materials Science The objective of this project is to create an engineering device that harvests environmental energy, mimicking the ballistospore fungi which discharge spores by the so-called one-shot microengines powered by surface energy. This biological process has been reproduced at Duke: coalescing condensate droplets on a superhydrophobic surface release surface energy, which is eventually converted to kinetic energy propelling the droplets to jump. The background is discussed in a news item in the magazine Science (https://web.duke.edu/uphyl/Science_Chen.pdf). This project is primarily experimental but will also involve the development of scaling laws. The student will have the opportunity to use high-speed photography to capture surface energy conversion process of ballistospore discharge at one million frames-per-second, and use the mechanistic understanding to guide the design and development of an engineering prototype that mimics this energy harvesting process. Project: #34: Nonlinear Aeroelasticity Advisor: Earl Dowell, Professor & Dean Emeritus, Mechanical Engin.& Materials Science Our research is concerned with the dynamic interaction of a fluid and an elastic structure, a field termed aeroelasticity, i.e., aerodynamics plus elasticity. Recent research has emphasized nonlinear aspects of the phenomena. Research has often been motivated by aerospace applications such as the oscillations of aircraft wings, turbine blades in jet engines, hypersonic inflatable aerodynamic decelerators (HIAD) and solar sails. However, we also study applications to biomedical engineering, e.g., blood flow through arteries or airflow through the mouth; civil engineering, e.g., wind loads on bridges and buildings; electrical engineering, e.g., wind induced oscillations of power lines; and to many other aspects of engineering. Current projects involve either theoretical or experimental research. These include the following: (1) dynamic response of airfoils and wings due to selfexcitation and external forces; (2) high performance airfoils; (3) wing planforms that deform as plates; (4) long span, highly flexible wings typical of uninhabited air vehicles; (5) novel geometries that lead to enhanced aeroelastic performance including oblique wings and folding wings; (6) control of and energy harvesting from such systems; (7) HIAD and (8) solar sails. Project # 35: Assembly and Actuation of Binary Colloidal Crystal Alloys Advisor: Ben Yellen, Associate Professor, Mechanical Engineering and Materials Science This research project will introduce undergraduate students to a materials science topic in soft matter physics. The REU student will work with the graduate student in my lab to assemble large crystals from a collection of micron-sized magnetic and non-magnetic colloidal particles that are immersed in a ferrofluid. When exposed to a uniform magnetic field, these particles interact with each other like opposite charges and form structures that resemble salt crystals. Due to the relatively large size of the particles, we are able to visualize and track each particle during the crystal formation and actuation process. These kinetic crystallization mechanisms serve as a good model for the formation of atomic crystalline domains, cracking, and other materials science problems. During the REU period, the student will be involved in the development of computer software to perform image tracking, and order correlations taken from video experiments, and will work closely with the graduate student to make fundamental discoveries in materials science. Projects #36 and #37: Laboratory of Dr. Stefan Zauscher (see below Project #37 for many project descriptions of students in Dr. Zauscher’s laboratory). Project #36: Biomacromolecular Block-Copolymers and Brushes Advisor: Stefan Zauscher, Sternberg Family Professor of Mechanical Engineering and Materials Science, Professor of Biomedical Engineering and of Chemistry Practical design of biologically inspired materials has large potential for positively impacting society's well-being, as biomolecular materials can deliver medical therapeutics, are employed in sensors to detect biological and chemical threats, and biomolecular nanostructures are used as scaffolds and templates to imbue novel function for inorganic materials. While most man-made polymeric materials serve structural purposes, they do lack precise sequence specificity and do not approach the functional sophistication of biomolecular materials. Biomolecules, however, provide structural and informational properties, whose functions are encoded within distinct sequences of diverse monomer sets. At present, however, there still is a lack of fundamental understanding to control or influence the hierarchical self assembly of biomolecular building blocks, although this step is critically necessary to unlock the potential of biomolecular materials. We have shown that the template-independent polymerase, terminal deoxynucleotidyl transferase (TdT) can catalyze the growth of ssDNA from a short oligonucleotide initiator attached to a surface or create high molecular weight (up to 8 kb) homopolymer and copolymer DNA in solution with exquisite control of chain lengths. Furthermore, we have shown that a broad range of unnatural nucleotides with unique chemical functionalities (biotin, amine, and aldehyde groups) can be directly incorporated into the ssDNA by TdT catalyzed synthesis. The use of TdT to create complex DNA based hybrid materials in situ from a range of substrates and from genetically engineered polypeptides, is a rich and untapped area of soft matter research that we will exploit in the framework of the newly established NSF Materials Research Science and Engineering Center (MRSEC) in Softmatter at Duke. For example, temperature-triggered microphase separation of diblock DNA-polypeptide copolymers could lead to micelles that consist of a hydrophobic core (polypeptide) and a hydrophilic shell (polynucleotide), and will depend on the relative size of the blocks and their relative difference in solvation properties. The REU student will engage with graduate students in the characterization of these biomacromolecular materials, including transmission electron microscopy, AFM, and Small Angle X-Ray Scattering. Project #37: Harnessing Bacteria for the Fabrication of Inorganic Materials Advisor: Stefan Zauscher, Sternberg Family Professor of Mechanical Engineering and Materials Science, Professor of Biomedical Engineering and of Chemistry In this project we seek to demonstrate that bacteria can be harnessed for the biosynthesis and deposition of semiconducting nanoparticles and thin films that have useful technological properties in areas as diverse as energy generation, microelectronics and biosensing. Specifically, we use engineered bacteria (You laboratory) to generate well controlled cadmium sulfide (CdS) particles and thin films. CdS thin films play an important role in photovoltaic technology and for optoelectronic devices. The currently used chemical bath deposition for the synthesis of CdS thin films remains, however, a continuing challenge. Here, biology may offer complementary, and possibly vastly better, options. The bacterial biosynthesis and precipitation of CdS nanocrystals intracellularly and extracellularly has been prototypically shown, and useful biochemical reduction pathways have been engineered. Here we harness engineered bacterial expression systems for the deposition of nanocrystalline CdS thin films and particles with core-shell morphology. The REU student will work with a graduate student on nanoparticle synthesis and characterization using advanced surface analytical tools, such as AFM, XPS, SEM. REU Students in Dr. Zauscher’s laboratory: Crystal Padilla, Sophomore, Biology Major, Gallaudet University Mentors: Professor Dr. Stefan Zauscher, Triangle Materials Research Science and Engineering Center (MRSEC), Kate Marusak, Ph.D student Project Title: Synthesis Cadmium Sulfur and Engineering Bacteria to Fabricate CdS Thin Film The purpose of this project was to utilize the ability of E. coli to precipitate cadmium sulfide (CdS) nanoparticles (NPs) for thin film development. Some of the things that were explored to accomplish this goal were varying the media (nutrients) for bacterial growth, testing out different precursors to precipitate the NPs, varying the amount of cadmium the bacteria was exposed to, optimizing the processing of the bacteria after particle precipitation, and characterizing the NPs using different equipment including transmission and scanning electron microscopy (TEM and SEM), UV-vis, X-ray photoelectron spectroscopy (XPS), and energy dispersive spectroscopy (EDS). Lysogeny broth (LB) experiments had already been conducted, so M9 was explored upon my arrival as another nutrient source for the bacteria to produce particles. Preliminary results show much better particle precipitation with the M9 medium. We also varied different precursors including K2SO4, CdCl2, IPTG, and cysteine. It was found that the presence of all these precursors aids in CdS production with the exception of K2SO4, which does not inhibit or increase NP formation. We also tested the optimal amount of cadmium to be introduced to our bacteria for particle formation. A high concentration of cadmium is toxic to the cells and will kill them; however low concentrations of cadmium does not produce high quantities NPs. A balance between these two concentrations was examined by testing 0.05, 0.075, 0.1, 0.125, 0.15, 0.175, 0.2 0.25 mmol of cadmium chloride. The results have shown so far that 0.1 mmol of CdCl2 is optimal. We also have been optimizing the particle extraction from the bacteria by investigating different processing/lysing conditions as well as filtration methods. Literature reports many different bacterial lysing techniques such as the use of tris-HCl buffer, ethanol, and SDS solutions in varying conditions including under ultrasonication and high temperatures. We have attempted all of these conditions, and our results indicate that tris-HCl buffer at high temperatures results in the best bacterial lysing. Our next step is to examine the best method of removing the bacterial debris so that only our CdS NPs remain. After, we plan to use the filtered NP solution to show NP concentration using UV-vis. Chelsie Stallings, Senior, Chemistry, Gallaudet University, Department of Chemistry Mentors: Stefan Zauscher, Professor of Mechanical Engineering and Materials Science, Professor of Biomedical Engineering and of Chemistry, and Zehra Parlak, Post-doctoral Fellow, Mechanical Engineering and Materials Science, Biochemistry Project Title: Investigation of Protein-A by QCM In this research, we describe a method to observe unfolding kinetics of surface proteins by quartz crystal microbalance (QCM) when they are tethered to a surface. Kinetic studies on the unfolding of surface proteins, such as Staphylococci aureus bacteria’s surface protein, protein-A, have been conducted in solutions so far, but these proteins are attached to surfaces in their natural state. In our method, we first use a protein solution to create a monolayer of protein on the gold electrode of QCM. Then, we induce unfolding of the protein by injecting guanidine chloride (GCl) solutions of varying concentrations. Since GCl solutions have high density and viscosity, traditional QCM systems cannot decouple unfolding of the proteins from the effects of the solutions. However, the recently introduced fluid density and viscosity compensated QCM method of Zauscher lab can decouple these two parameters and observe protein unfolding. In this study, we verified the fluid density and viscosity compensated QCM method by using glycerol solutions of different concentrations, which solely changes the fluid properties. We measured protein-A adsorption kinetics on the gold surface of QCM and we compensated fluid properties during the introduction of GCl. We were able to observe conformational changes of the protein-A on the surface by using this compensation method. Jesse Fuller, Chemistry Major, Gallaudet University Brushes on a Lead Zirconium Titanate (PZT) Jesse Fuller is a chemistry major from Gallaudet University. His project objective was to create end-tethered polymer brushes grafted from lead zirconium titanate [Pb (Zr0.48Ti0.52)O3] surfaces. By first forming monolayers on PZT, followed by surface initiated polymerization, our findings present the results of the polymer brush properties on PZT using Atomic Force Microscopy (AFM) in a contact mode. This research outlines, for the first time, how using traditional grafted from polymerization conditions is able to grow N-isopropylacrylamide polymer brushes on PZT Stimulus response characterization was performed in a variety of environments including, 100% deionized water and 50% deionized water/50% methanol. The polymer brushes in 100% deionized water responded with the highest length in brush height. Joshua Doudt, Chemistry, Gallaudet University Changing the Crystal Structure of PZT Thin Films with Self-Assembled Monolayers Joshua Doudt is a senior chemistry major at Gallaudet University. In 1983, Nuzzo and Allara used alkanethiol molecules to form Self-Assembled Monolayers (SAMs) on a gold substrate. Ever since this discovery, many different researchers have used monolayers for a wide variety of applications. The goal of this project is to recognize the effect of SAM to change the surface properties of Pt to influence Lead Zironcate Titanate (PZT) crystal structure. SAMs is single layer of organic molecules. It will form spontaneously through adsorb on any types of the substrate such as metals, semiconductors, or insulators. For this project we will use platinum coated silicon wafer as our substrate. The SAMs will be using in this project to aiding the development of PZT crystal structure through heating process. The procedure of developing sol gel PZT will be making through spinning coat process. The result of PZT crystalline will be developed when it is heated up to specific temperature for thirty minutes. The X-Ray Diffraction measured the PZT crystalline peak in the order to recognize the PZT crystal structure. The results showed that SAMs changed the surface properties of Pt to influenced the PZT crystal structure yet, the SAMs didn’t give us great PZT (100), (110), and (111) crystal structure. Alexander Matsche, Chemistry Major, Senior, Gallaudet University Single Molecule Force Spectroscopy of Lubricin Alexander Matsche is a chemistry major and senior from Gallaudet University. The objective of his research was to collect evidence in support of the hypothesis that reduced lubricin shows different mechanical behavior due to pH induced alterations in its conformational state. The nanomechanical properties were measured by single molecular force spectroscopy with an Atomic Force Microscope. The results of studies of a single molecule of reduced lubricin prove that a molecule with a pH 4.1 has less force and distance than one with a pH 7.4. Also, the molecule with pH 4.1 is more flexible with regard to persistence distance than is the molecule with pH 7.4. These results show that various pH’s do affect the lubricin’s behavior with regard to force, pull off distance, contour length, and persistence length, and are significant with regard to research into joint problems in the future. During his research, Alex learned many new procedures in Single Molecule Force Spectroscopy. REU Fellow: Alexander Matsche, Chemistry, Junior, Gallaudet University The Influence of Relative Humidity on Particulate Interactions in Carrier-Based Dry Powder Inhaler Formulations Alex Matsche is a chemistry major from Gallaudet University. The goal of his project was to study the adhesion between the carrier and the active ingredients for an asthma drug called AdvairTM, a dry-powder inhaler containing Fluticasone Propionate, Salmeterol Xinofoate, and Lactose . Alex’s hypothesis was that dry air had a more positive effect on the adhesion force between the drugs and the carrier, and that the amount of humidity can make a big difference in the adhesion force between the active ingredients and carrier. If a certain level of humidity does indeed make a big positive difference, then this result can help improve the drug’s manufacture and use as an asthma medicine. The Atomic Force Microscope can read and measure the topography and adhesion force from smooth surfaces with a cantilever probe technique. An Atomic Force Microscope with a humidity control chamber is used to investigate the effect of relative humidity from 5% to 90% to measure the adhesion force of the recrystallized drugs. The difference in humidity between dry and humid air can make a big difference in the adhesion force of the active ingredients and carrier. An X-Ray Photoelectron Spectrometer is used to study and compare the chemical structure of the original powder drugs and the recrystallized drugs before we test them in the Atomic Force Microscope. The adhesion force will be measured on the recrystallized drugs’ surfaces by placing a lactose coated, tiny crystal of the recrystallized drugs on the cantilever’s tip. The Scanning Electron Microscope is used to measure the tiny crystal on cantilever’s tip. The results showed that the humidity of the air does affect adhesion force of each drug. These results can lead to improvements for asthma medicine users and for the manufacture of drugs by pharmacology companies using the correct humidity control in the factory. John Thuahnai, Biology Major, Gallaudet University Project: Friction Behavior of Stimulus-Responsive Hydrogels The purpose of this research project is to study the friction behavior of stimulus-responsive hydrogels at three different levels of cross-link density (high, medium, and low). This project also explores the gel preparations with different cross-link density by adding N’N-methylene-acrylamide (MBAAm). The hypothesis was “high” cross-link density gel would handle shear strain rate more than “low” cross-link density gel. The friction measurements were obtained with controlled strain rheometer. To report the coefficient of friction, we need a measure of normal force, which requires normal load cell to be installed in the rheometer. However, load cell was not available so we could only report the friction force (Ff = t * r^2/2). Measurements were performed with shear rates with gel sliding against the metal surface of the measurement geometry. “High” and “medium” cross-link density gels proved to be only feasibility for this experiment. Low cross-link density gels were unstable in this experiment. Despite failure of low cross-link density gel, the result proved the hypothesis to be acceptable. REU Fellow: Lucas Barrett, Mathematics Major, Gallaudet University Project: PNIPAAM Contact Angles as a Function of Temperature In his project, Lucas hypothesized that contact angles will change as a result in temperatures, with some being hydrophobic and others being hydrophilic. The goniometer experiments were to determine temperature to contact angle graph for the prepared samples. The experiments were unable to determine a graph that validates the current pNIPAAM LCST graph. The primary reason was that there is little material published regarding pNIPAAM and its effect on contact angles. PNIPAAM is widely used because of its ease of use. S. Balamurugan, et al, gives the theoretical LCST graph of pNIPAAM in a published paper but the paper does not give much detail into their methods as to how they developed their data. In addition, Lucas suffered numerous equipment failures ranging from power and temperature loss to problematic wiring. Lucas was forced to develop many different possible strategies of angle measurement. For example, he attempted to saturate the ambient atmosphere around the samples in regards to humidity; he left the samples to stabilize at a set temperature on the stage for a period of 20 minutes for each temperature. Lucas placed the stage at an angle to force the sessile drops to move minutely to determine advancing and receding angles. He heated the water from which he made his sessile drops. He soaked the samples overnight to re-hydrate the polymer brush, in case it collapsed. The second possibility could be that Lucas’s samples were not adequately clean. It could be that contamination of the sample neutralized the pNIPAAM. Despite all these different attempts, he found no significant difference in angles as the temperature moves across the LCST region Pia Marie Paulone, Biology Major, Gallaudet University Adhesion between Carrier and Active Ingredients in Dry-Powder Inhaler Formulations Measured by Single Molecule Force Spectroscopy Pia Marie Paulone is a biology major from Gallaudet University whose project involved the adhesion between carrier and active ingredients in inhaler formulations. The formulation of Advair™ includes two drugs, Fluticasone Propionate (FP) and Salmeterol Xinofoate (XP), and an inactive lactose carrier. Production of Advair™ includes an extremely short initial mixing time, but requires a longer amount of time to ensure that drug particles are sufficiently bound to the carrier particles. Understanding and quantifying adhesion forces between the drug and lactose using single molecule force spectroscopy (SMFM) will lead to improved efficiency in production lines. Model surfaces composed of dissolved drug and dissolved lactose are created and coated on two surfaces: a cleaned glass slide and a 10 micron borosilicate glass bead mounted on the tip of an Atomic Force Microscope (AFM) cantilever with the ultimate goal of accurately mimicking adhesion behavior between the two substances. Based on data acquired from both AFM and Scanning Electron Microscope (SEM), it is known that lactose and FP interaction is of far greater magnitude than either glass on glass interaction or lactose on glass interaction. This presents a definite confirmation of the feasibility of the preliminary material system.