Abstract Submitted for Presentation

Zeal Jinwala1, David Haruch2, Swathi Swaminathan2, Alisa Morss Clyne2 1Department of Biology, Drexel University, Philadelphia 19104, 2Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia 19104

Harvard National Collegiate Research Conference- Cambridge, 2019

Endothelial cells (ECs) line the interior surface of blood vessels and drive angiogenesis, the process of new blood vessel formation from existing blood vessels. Angiogenesis is thought to be a critical factor in tumor growth [1]. Angiogenesis occurs through a complex, 3D process of endothelial proliferation, migration, and eventual maturation into a blood vessel. Recently, EC metabolic activity has been shown to be important to angiogenic sprouting [2]. For this project, we decided to test two metabolic inhibitors, namely 3PO and OGTi, in an endothelial tube formation assay to determine their effects on angiogenesis. 3PO is known to inhibit glycolytic activity, and OGTi decreases protein O-GlcNAcylation through the hexosamine biosynthetic pathway. The goal of this study was to evaluate the effect of these two inhibitors and understand the use of these inhibitory mechanisms in angiogenic sprouting in ECs.

Ewing sarcoma (EWS) is a rare and highly aggressive cancer arising in both bone and soft tissue that mainly affects children, adolescents, and young adults. EWS has a 70-80% survival rate for patients with localized disease, which drastically reduces to ~30% upon disease progression to a metastatic state. EWS is characterized by the fusion of a FET gene family and an ETS transcription factor—the most common being EWS-FLI1 (~85% of all EWS). Utilizing genetic, epigenetic, and bioinformatics tools, a novel and highly specific EWS-FLI1 regulated gene, LOXHD1, with a potential oncogenic role was previously discovered by my lab group. Since solid tumors, like EWS, have been known to develop a hypoxic microenvironment—which quite often leads the cancer cells to metastasize and migrate to other parts of the human body—I hypothesized that preventing hypoxic microenvironment by inhibiting LOXHD1 can reduce the metastatic potential of EWS. The CRISPR dCas9-KRAB system was first used to repress the transcriptional activity ofLOXHD1 in two EWS cell lines, SK-N-MC and RD-ES. Upon hypoxia treatment, these knockdown cells underwent RNA-seq and gene set enrichment analysis (GSEA), which showed a very weak hypoxic stress response and a strong negative enrichment for the Hallmark Hypoxia signature. Western blot analysis further showed a decrease in HIF1α (a hallmark of cellular hypoxic-stress response) protein expression. Furthermore, immunofluorescent staining of F-actin in the knockdown cells showed highly disorganized and chaotic actin filaments, and cell invasion and migration assays demonstrated a ~2-fold reduction in invasion potential—thus, highlighting the role of LOXHD1 as a regulator of cytoskeletal assembly and metastasis. Overall, these in vitro studies showed that LOXHD1 plays a significant role in Ewing sarcoma metastasis in hypoxic conditions.

Mid-Atlantic Undergraduate Research Conference – Virginia Tech
March 28, 2020
Poster Presentation
The Knockdown of HSC 70-3, Cyp1, Cnx99a, Rok, and PDGFRB and its Effect on Early Cognition in Drosophila

Alzheimer’s Disease (AD) is a neurodegenerative disorder that causes a deficit in a person’s learning and memory. This disease is caused by cell death where the tissue contains fewer nerves and connections in comparison to a “healthy brain”. When the Amyloid Precursor Protein (APP) in human brain cells are improperly cleaved, A-Beta (Aꞵ) fragments are generated which result in Aꞵ plaques. These plaques are a well-recognized marker for AD in human brains. In this work, we examined the effects of five separate APP drosophila genes through behavioral, learning, and memory assays on their larvae.
HSC 70-3, Cyp1, Cnx99a, Rok, and PDGFRB are drosophila genes with human homologs that show a strong correlation to AD. The gene HSC 70-3 plays a supportive role in the progression of tau phosphorylation (a hallmark of AD) and neurodegeneration. Cyp1 is involved with Traumatic Brain Injuries (TBIs) and cell death in neurons. Cnx99a is found in patients diagnosed with AD. In addition, the expression of Rok and a mutation in PDGFRB may be implicated in AD onset; both genes cause cell death and glial scarring after TBIs, which are known to increase the risk of developing early-onset AD. By examining these two genes, we gain perspective into a possible correlation between TBIs and early-onset AD. Using genes identified in both our lab’s RNA sequencing data from a well-characterized AD model fly and RNA sequencing data from human TBI patients, we investigated if the knockdown of these genes played a role in early cognition in larvae

Stanford Research Conference
Application to Present
April 5-7, 2019
Was not accepted

Title:
Effect of Shear Rate and Drying Speed in Lithium-Ion Battery Slurry Processing  

Abstract:
Processing conditions of battery slurries into electrodes are known to affect final battery performance. However, there is a lack of fundamental understanding of how to control processing conditions to achieve better batteries. Previous work has focused on the formulation step of the battery manufacturing process. This study concentrates on two of the slurry processing steps, namely coating and drying, and their effect on film quality and coin cell performance. Rheological measurements were used to determine the starting slurry microstructure as well as determining the effect of flow on microstructure evolution. Well-characterized slurries were subjected to a series of shear rates and drying temperatures to examine the effect of flow and drying rate on final cell performance. The data suggests that there is a complex relationship between surface roughness and shear rate/temperature, but ultimately, performance based on shear rate is dependent on drying time. Wet slurries are well mixed to form homogeneous suspensions. The slurries are spread via an automatic bird applicator coater to the desired thickness. The film is quickly exposed to different baking temperatures to remove solvent. We observe that higher temperatures produce better performing batteries on average. We argue that quicker drying times prevent sedimentation and phase separation of the slurry. By using scanning electron microscopy images and energy dispersive spectroscopy maps, a Matlab program was written to characterize final performance according to particle and chemical species dispersion. The shear rate has a unique influence on the final cell performance, and the optimum shear rate depends on the temperature of drying. Coin cells are cycled at varying capacity rates, and overall discharge capacities were analyzed in accordance with EDS elemental maps to define the suggested relationships. While more data is needed to make concrete conclusions, the preliminary data presented here shows for the first-time quantitative relationships between processing conditions and battery performance.

NCRC 2018
January 18-20, 2018
Poster Presentation

Title:
Effect of Shear Rate and Drying Speed during Battery Electrode Processing

Abstract:
Processing conditions of battery slurries into electrodes are known to affect final battery performance. However, there is a lack of fundamental understanding of how to control processing conditions to achieve better batteries. Previous work has focused on the formulation step of the battery manufacturing process. This study concentrates on two of the slurry processing steps, namely coating and drying, and their effect on film quality and electrode performance. Rheological measurements were used to determine the starting slurry microstructure as well as determining the effect of flow on microstructure evolution. Well-characterized slurries were subjected to a series of shear rates and drying temperatures to examine the effect of flow and drying rate on final electrode performance. The data suggests that there is a complex relationship between surface roughness and shear rate/temperature, but ultimately, performance based on shear rate is dependent on drying time. While more data is needed to make concrete conclusions, the preliminary data presented here shows for the first time quantitative relationships between processing conditions and battery performance.

The onset of the COVID-19 pandemic prompted an unprecedented demand for medical equipment capable of combating the effects of acute respiratory failure. Health care systems worldwide were found ill-equipped to handle the sheer volume of patients exhibiting the respiratory issues associated with this novel strand of the coronavirus, often requiring methods of assisted breathing. This project was initiated amidst the worldwide shortage of mechanical ventilators with the goal of designing, manufacturing, and testing a portable, inexpensive, and automated respiratory support device that utilizes an FDA approved bag valve mask (e.g., Ambu bag) to mechanically assist patient breathing.

The foundation of this project was initialized with a mechanical understanding of the problem. The manual bag valve mask resuscitator is an alternative solution to the traditional, expensive, and complex method of mechanical ventilators. Medical personnel repeatedly provide manual compressive action on the bag to assist a patient that is exhibiting respiratory issues. To alleviate the manual requirement from this process, a mechanized compression gantry was designed to create an automated and programmable operation. The device’s contribution to the engineering and medical fields lies in the process with which it was developed. The employed design process incorporated a digital and distributed manufacturing approach that streamlined design iterations and maximized productivity. Managing the design process in the digital environment enabled the team to capture design history and relevant design decisions. The team also integrated product lifecycle management (PLM) tools to document each avenue that was pursued to achieve the final device. This process augmented traditional design and prototyping methods with an approach that conceptualizes and validates the design in the digital environment prior to manufacturing.

To effectively utilize this streamlined digital design process, each custom component was run through three interconnected phases: Design, Simulation, and Optimization. Following the conceptualization of the component design, computational analysis tools were used to validate the design’s ability to handle the anticipated loads. These load cases were determined through experimentation and implemented in the digital design workflow. With the validated design, simulation results were used to identify components as candidates for optimization processes in a final refinement phase. This phase was used to uniquely produce parts that capitalized on the robust capabilities of additive manufacturing processes. Despite initiating this project on a mechanical thread, the biomedical aspects were progressively weaved into the design process. Experiments were developed around the design to test the device’s ability to meet regulatory requirements. As this is an electromechanical device, even the electrical components of the design were first assembled in CAD prior to physically purchasing the parts.

The outcome of implementing this rapid digital design process was a completed and manufactured prototype that was ready for testing within a month after the project launch. The design evolved with each test where multiple components were consolidated into single parts, custom components were redesigned for quicker manufacturing, and optimization tools were used to reduce the physical footprint of the device. Using computational analysis tools and creating digital assemblies reduced the number of transitions required between the digital and physical workspaces. Efforts have already been devoted to creating a second version of the device to be more compact and easier to manufacture. This project was an exercise in a deadline-enforced product design process for a real-world application. The team employed streamlined digital design techniques to design, validate, and optimize the device for efficient manufacturing and testing.

It is known that long waves in spatially periodic polymer Fermi-Pasta-Ulam-Tsingou lattices are well-approximated for long, but not infinite, times by suitably scaled solutions of Korteweg-de Vries equations. It is also known that dimer FPUT lattices possess nanopteron solutions, i.e., traveling wave solutions which are the superposition of a KdV-like solitary wave and a very small amplitude ripple. Such solutions have infinite mechanical energy. In this article we investigate numerically what happens over very long time scales (longer than the time of validity for the KdV approximation) to solutions of diatomic FPUT which are initially suitably scaled (finite energy) KdV solitary waves. That is we omit the ripple. What we find is that the solitary wave continuously leaves behind a very small amplitude “oscillatory wake.” This periodic tail saps energy from the solitary wave at a very slow (numerically sub-exponential) rate. We take this as evidence that the diatomic FPUT “solitary wave” is in fact quasi-stationary or metastable.

The work presented at this conference was my STAR Research.

Understanding the relationship between ovary development and dominance in a eusocial tropical paper wasp (Mischocyttarus pallidipectus)

In primitively eusocial Mischocyttarus pallidipectus paper wasp colonies, separation of members into reproductive castes is characteristic. Unlike many insects which are divided into morphologically and functionally distinct castes, M. pallidipectus castes are monomorphic: females on the nest are identical at emergence but will differentiate into castes by social dominance. The July 2019 field season in Monteverde, Costa Rica was devoted to testing the hypothesis that ovary size is correlated positively with dominance and connecting this to differences in individual chemical cues. In the field, I worked alongside a small team of researchers to locate wasp nests and observe individual wasp behavior for four hours each day over two days to identify dominance interactions and determine the social hierarchy of females. Following observations, the wasps were collected, and females were dissected. Female ovaries were photographed and measured in order to examine the behavioral data against the size and development of their ovaries. The gasters of each wasp were swabbed for their cuticular hydrocarbons which were then run on chromatography columns, allowing us to evaluate whether there is a difference in the chemical identity of females with and without developed ovaries. Through this research, we show that female dominance increases with ovary development and that the most dominant females encountered significantly more interactions than filamentous females and males with members on the nest that increased their opportunity for better nutrition that would continue to facilitate their development. 

Event: CoAS Research Day

Presentation: Medical Students' Strategies for Standardized Tests of Communication 

Date: 2020
Type: Judged Presentation

Abstract Title: Medical Students' Strategies for Standardized Tests of Communication 
          The use of standardized patients (SPs) is now common and widespread in medical schools in the United States. While these encounters are artificial, they provide important opportunities for medical students to practice social skills related to patient-physician interactions. And yet, because these encounters are evaluated using standardized metrics, medical students are aware of the need to perform to the test in such an artificial setting. This becomes interesting for sociologists, as these encounters deal with questions of empathetic communication and emotional engagement, which are intersubjective. How do medical students understand these requirements? In this paper, we analyze one years’ worth of posts from Reddit and StudentDoctorNetwork to understand the ways in which medical students account for their performances of emotional labor in standardized testing contexts. We find that students are aware of the gap between expectations within testing standards and those of the clinic, and that students have routinized strategies for passing the test.  

Amphibians have been experiencing extinctions and declines at unprecedented rates, and as ectotherms, they may be particularly sensitive to environmental changes. Determining the best way to predict body temperatures in the field is a critical tool to better understanding the adverse impacts of environmental changes on this imperiled taxon. Using agar models, mechanistic niche modelling, and field collected data, we attempted to accurately model the range of body temperatures that Green frogs, Lithobates (Rana) clamitans, a semi-aquatic species, may experience at three sites in Northwestern Pennsylvania. Agar models containing temperature loggers were deployed, and plasti-dip was utilized to create permeable and non-permeable models to encompass the potential range of cutaneous water loss seen in nature. We then employed the program Niche Mapper™ to model the body temperatures of amphibians in their environment utilizing data on microclimate and amphibian physiology. Both night and day surveys were also conducted to collect actual frog body temperatures using non-contact infrared thermometers. Temperatures experienced by agar models were greatly influenced by model permeability, despite occupying similar microhabitats. These data in conjunction with Niche Mapper™ projections provided an encompassing gradient for temperatures of live anurans. Moving forward we are working to refine both environmental and physiological Niche Mapper™ parameters to improve the accuracy of predicted frog body temperatures further. Ultimately, the ability to model amphibian body temperatures will allow us to predict changes in behavior, physiology and potentially also disease risk in response to changes in the environment.  

(This is the same abstract submitted for my on-campus presentation)

Ozone is recognized as a safe and powerful disinfectant in water that leaves no harmful residuals because it rapidly decays into oxygen. The current method of ozone generation is cold corona discharge, which is unfavorable because it creates harmful nitrogen oxides in air and yields low concentrations of ozone when dissolved in water, lowering operational efficiency. A possible solution to this problem is generating ozone electrochemically, which can be done by choosing electrode materials that are much more selective in oxidizing water into ozone than oxygen. Nickel- and antimony-doped tin dioxide (NATO) has proven to be an electrode material active for ozone generation; however, its current efficiency (i.e. selectivity of ozone instead of oxygen) has not exceeded 50% in literature [1] and the material has poor stability.  

Typically, NATO electrodes are synthesized as a sol-gel from a coating of metal precursors decomposed thermally in air. In this study, we electrodeposit thin films of NATO to control catalyst loading and compare the effects of synthetic routes on the ozone generation reaction. From baths containing either chloride or nitrate ions, we deposit either metallic or oxide films. With chloride ions, Sn(II) is reduced directly to Sn(0) on the substrate, and then is thermally oxidized to SnO2. With nitrate ions, reduction of nitrate ions increases local pH and causes SnO to precipitate onto the substrate. The films are characterized by X-ray diffraction and Scanning Electron Microscopy/Energy Dispersive X-ray analysis, and ozone selectivity is measured with spectroelectrochemistry. We observe that thermal oxidation yields higher current efficiencies than electrochemical oxidation. Annealing time does not affect ozone current efficiency, but high annealing temperatures increase both SnO2 crystallinity and ozone current efficiency. Increasing the concentration of Sb and Ni in the electrodeposition bath increases both the amount of dopant present and the ozone current efficiency.  This electrodeposited NATO synthesis method has yet to be optimized, but achieves ozone current efficiencies of 35-45%, comparable to the sol-gel method. Efforts to relate the structural and material properties of NATO to ozone selectivity and activity are ongoing.

Sources: [1]. Christensen, P. A. “Room Temperature, Electrochemical Generation of Ozone with 50% Current Efficiency in 0.5M Sulfuric Acid at Cell Voltages < 3V.” Ozone: Science and Engineering, no. 31, 2009, pp. 287–293., doi:10.1080/01919510903039309.