Polymeric micelles are nanoscopic structures constructed with amphiphilic diblock copolymers constructed with hydrophobic and hydrophillic portions that spontaneously form micelles in solution. Small hydrophobic molecules, such as cancer drugs taxol and doxorubicin, can be encapsulated in the micelle, which effectively serves as a nanovehicle for drug delivery. Here, we will develop a diblock copolymer integrating polyurethane-based self-immolative polymers (SIPs). SIPs are polymers that sequentially disassemble into their building blocks once the disassembly process is initiated by a triggering event at the trigger head group. By using SIPs, the polymers that make up the micelle are designed to depolymerize which we hope to increase the efficacy of payload release and remove the ability for micelle reformation. For this project, the micelle and all parts of the system will be synthesized from the bottom-up; optimizing the molecular weight of the diblock for micelle formation, investigating the kinetics of depolymerization and thermal trigger activation, and examining the stability of the micelle.

Antibiotic resistance is a challenging problem in the realm of human health today. As a fundamental evolutionary phenomenon, it provides an excellent system to test adaptive evolutionary theories in a short amount of time. Thus, I explored the rise of antibiotic resistance in two evolution experiments with Escherichia coli. In the first, I asked how differences in genetic background affect the rate of adaptation to a new environment. To address this question, I generated 19 unique antibiotic resistant mutants by evolving E. coli in an environment with low drug concentration, and then exposed thousands of populations of each isolate to a high concentration environment measuring the proportion of populations that survived. Since survival in the high-drug environment requires acquisition of a new beneficial mutation, I hypothesized that high mutant survivorship indicated an isolate with more mutational options available in the high drug environment (we call this “potentiation”). Isolates with low survivorship would have fewer available mutational options (we call this “doom”). Interestingly enough, some observed differences may be due to a phenomenon known as sign genetic epistasis – when mutations have different effects in combination than individually. Preliminary data suggests a few strong cases for potentiation. I also investigated the effect of an initial resistance mutation on the consequent adaptations in a no drug concentration environment. To study this, I generated 23 unique mutants of E. coli and tracked how fitness and drug resistance changed over time in 2,200 populations. Both of these experiments help illuminate the role of historical contingency in evolution, the idea that an initial mutation may dictate an organism’s future mutational trajectory (available mutational options). Therefore, understanding both the effect of initial mutations and the underlying mechanisms of mutation acquisition is necessary in order to combat the emergence of resistant bacteria, a current human health concern.

Dyslexia is a complex disorder that interferes with a person's ability to read and spell with no consensus as to what causes it. The typical person processes language in the left hemisphere and is either right or left handed while very few people have ambidextrous tendencies. Our hypotheses are two-fold. First, that competition between the brain's two hemispheres underlies dyslexia. Second, that this competition is evident in cortical activation during reading tasks as well as performance speeds during hand motor tasks. To test our hypotheses, we collected data from 52 adult participants (19 with dyslexia, 33 controls) who underwent electroencephalography (EEG) measures during a word reading task and also performed an alternating keytapping task.To investigate Hypothesis 1 (lack of lateralization is associated with dyslexia), we categorized our participants' EEG data according to typically vs atypically lateralized language activation patterns. Higher than expected numbers of adults with dyslexia in the atypical hemisphere activation group would be consistent with our hypothesis. To investigate Hypothesis 2 (correlations between the two modalities), we calculated a relative lateralization score for each of these task types and tested the correlation between these two scores for significance. Evidence of correlations between these two measures would yield higher than expected numbers of participants with dyslexia in the ambidextrous group as well. Evidence for both of our hypotheses will provide important insights into the biological underpinnings of dyslexia, pointing to disorganized brain circuitry in affected individuals. 

Binary chromophore systems contribute to more favorable intermolecular interactions and can significantly enhance electro-optic (EO) activity of EO materials, which have potential applications for telecommunications. Optimization of EO activity of binary chromophore systems consisting of dendrimer host (i.e. PSLD-33) and guest chromophore (i.e. FTC) will be achieved by determining the ideal host to guest concentration ratio. Synthetic schemes for known dendritic systems were proposed and synthesis is currently underway. Linear optical properties, including max absorbance (λmax) and molar absorptivity (ε), of materials in solutions with chloroform will be characterized using UV-vis spectroscopy. These properties have implications in chromophore packing density, which up to a thresh hold can improve EO activity. Additional steps include making films of the materials. EO activity of the materials will be characterized using the Teng-Man method, which has proven to be a convenient way to determine the EO coefficient (r33) in the Dalton lab over the past ten years.

The pancreatic islet β-cell secretes insulin in response to nutrients such as glucose. In type 2 diabetes, insulin secretion by β-cells is impaired, causing hyperglycemia. Our group investigates this impairment, with the goal of identifying and understanding the underlying mechanisms. Pancreatic islets contain an extensive capillary network, including endothelial cells, which produce soluble factors that may modulate β-cell function. Specifically, our group has shown that media from islet endothelial cells cultured under control conditions (5.5 mM glucose) and subsequently incubated with islets enhances insulin secretion from those islets. In contrast, media from islet endothelial cells cultured in diabetic conditions (high glucose; 25 mM) shows no effect on insulin secretion. Thus, we hypothesize that islet endothelial cells normally secrete paracrine factor(s) – signaling molecules produced by one cell that cause particular reactions in nearby cells – that enhance glucose-stimulated insulin release but that in diabetes, production of these paracrine factor(s) is reduced. The goal of this project is to identify one or more of these paracrine factors. We cultured islet endothelial cells under control and diabetic conditions. mRNA was extracted and sent for whole transcriptome analysis (RNA-Seq), creating an expression profile showing the expression amplitude for each gene. Analysis of RNA-Seq data revealed patterns of differential gene expression between control and diabetic samples. Changes in expression for genes of interest identified by RNA-Seq are being verified by quantitative real time PCR (qPCR). Subsequent protein analysis via ELISA or western blot will confirm the RNA-Seq and qPCR data. Viral vectors or siRNA will be used to either overexpress or silence respectively the gene(s) of interest in islet endothelial cells. Media will be collected from these cells and used on islets to determine its effect on glucose-stimulated insulin release. This project should reveal novel mechanisms by which islet endothelial cells influence insulin release.

 Over 90% of cancer-related death is caused by metastasis of invasive cells from one organ to another. Discovering more about this proliferative capability will be influential in creating new cancer therapies that will not only diagnose cancer, but may soon eventually fight it. Cancer metastasis involves migration of cells along bundles of extracellular matrix (ECM) fibers. In this context, understanding topotaxis through various kinase pathways which regulate cell migration is essential. An example of a kinase pathway is the PI3K pathway, one of the most mutated and well-studied pathways. When this pathway is over-expressed, proliferation of cancer cells is increased, while apoptosis of the cells is decreased. Additionally, cancer cells exhibit a more rigid nature suggesting that there are durotaxis involved for metastasis. Understanding these two mechanotaxes and how a particular oncogene influences the cellular response to these factors are vital in our quest to understand the process of cancer invasion. In our experiment, we studied two specific oncogenes in this pathway: PIK3CA and PTEN. Since PIK3A and PTEN are up-regulators and down-regulators of the PI3K pathway respectively, they will be an excellent model to investigate how PI3K is regulated by oncogenes. We hypothesize that cells not containing the down-regulated PTEN oncogene (knockout) and cells containing up-regulated PIK3CA oncogene (knock-in) will result in directional cell migration and increased migration speed and persistence time. To test this hypothesis, we utilized nano-scaled platforms of increased stiffness to simulate the ECM collagen fibers found on cancer micro-environments. Coupled with polymers such as polyurethane acrylate, polydimethyl siloxane, and poly(lactic-co-glycolic) acid, these platforms can vary the stiffness of cancer microenvironments, ranging from kiloPascals of normal tissue to gigaPascals of cancerous tissue. Thus, these platforms give us the opportunity to design a cancer tissue model to study effects of oncogenes on cancer invasion.

Targeted Tutoring is a program designed by our writing center to support English language learners in reading- and writing-intensive courses. The program was first piloted in 2010-2011 in response to students’ requests and to provide a space to encourage peer conversation. Targeted Tutoring is currently offered for courses in departments including English, Philosophy, International Studies, and Political Science. In Targeted Tutoring, three to five students meet for weekly sessions in which the tutor facilitates peer discussion. Group tutoring sessions are qualitatively different from the Center’s usual one-to-one sessions and tutors need to learn and apply new skills. This project is designed to further develop training for tutors, investigate effective models of group tutoring strategies, and explore what the differences and similarities are in skills useful in one-to-one sessions vs. those useful in group discussions. This research will be conducted by observing group sessions, crafting transcripts of successful group interactions in these sessions, and interviewing tutors and students to discover which strategies are effective. The project will be presented in a poster format that will include the models, guides, and strategies found to be most useful for tutor training and group facilitation. These results have significance for all those interested in peer education models and more effective small-group, discussion-based learning.

Photothermal heating of nanoparticles by electromagnetic radiation, which has potential applications including cancer treatment, requires consideration of the the electric field produced inside the nanoparticles. For most particle geometries, the electric field cannot be solved for exactly, so numerical methods are required. One such method is the Discrete Dipole Approximation (DDA), which models a target as an array of interacting point dipoles whose polarizations can be solved for. In this research, the DDA is used to simulate the electric field inside silicon and gold nanoparticles with spherical morphology. Particle sizes simulated range from 100 nm to 1000 nm, with a wavelength of 1000 nm. It is found that the particles exhibit morphology dependent resonance (MDR) at certain sizes. This is indicated by an increased electric field strength relative to the incoming wave, as well as an electric field  pattern corresponding to constructive reflection in the spheres. These resonances would lead to increased heating if the particles were used for photothermal applications.

Childhood Apraxia of Speech (CAS) is a rare, severe, persistent pediatric motor speech disorder of largely unknown genetic cause that affects the ability to acquire intelligible speech and coordinate the volitional production of sounds by sequencing muscle movements for the production of words. Developmental Dyslexia is a common and specific childhood learning disorder defined as a significant impairment in reading ability that cannot be explained by deficits in intelligence, learning opportunity, motivation, or sensory acuity. Various dyslexia studies suggest that slowed global processing speed, especially when sequential modes are involved, may be a brain-based endophenotype of dyslexia under genetic control. Impaired sequential processing, hence, may be a biomarker shared by CAS and Developmental Dyslexia. Our group recently identified a de novo heterozygous deletion of a single gene in a proband with severe CAS, raising the question whether similar deletions are causal in other cases as well. Here we report a genome-wide Single-Nucleotide Polymorphism (SNP) and CNV findings in a cohort of 20 affected individuals in nine multigenerational families with well-characterized CAS and six unrelated individuals with Developmental Dyslexia. All participants met clinical research criteria for CAS as part of a larger study on familial motor speech sound disorder or Developmental Dyslexia. The genome-wide copy-number variation study of the selected individuals was completed using the Illumina HumanOmniExpress-24 BeadChips and Human Exome BeadChips. Analysis of the SNP content and CNV for overlapping variations across the genomes of these affected individuals give us insight into genomic regions associated with the clinical phenotype of sequential processing deficit in multiple domains.

As social movements, technology, and political periods change through time, so does the young adult and their personal values. However, since the industrialization of the United States, one of the most enduring facets of American society is its system of capitalism and the overemphasis on having, or striving for, a materialistic lifestyle. With that being said, it has been found that one of the major drivers of change in personal values is materialism, and my study shows what effects materialism has on peoples' life goals and what life goals my sample has. The purpose of my study is to explore, using a convenience sample of Bemidji State University (BSU) students, how a materialist identity (or lack thereof) affects BSU underclassmen life goals (such as private wealth, self-fulfillment, family life, and public interest), using the 1991 Easterlin and Crimmins study for comparison, and as a way to see how levels of materialism have changed over time.

The aim of my presentation is to explore a unique approach to cinema called ‘a cinema of transvergence,’ as theorized by Will Higbee, as a means to glean the effectiveness of the work of three women directors from the Middle East/North Africa region, in suggesting possibilities for challenging the fixed positionings typically offered by the hegemonic structures of knowledge and power. When applied to the films of directors Raja Amari, Annemarie Jacir and Samira Makhmalbaf, a transvergent approach provides an open ended framework for understanding of interconnections which bind the filmmaker to a given film culture/national identity, the intentions, approaches and material conditions behind the production of their films, and the international reception of these films. The understanding of these factors, in turn, reveals the difference and imbalances of power exist between various film cultures and film industries.

Glacial advances and retreats are largely responsible for the current landscape of the Puget Lowland. Of interest to this study was a period of glacial retreat 15-60 thousand years ago. Nonglacial sediments deposited during this time, known as the Olympia Beds, are discontinuous throughout the South-Central Puget Sound region. Here we attempt to correlate between discontinuous outcrops of Olympia Beds based on mineralogy. Sediment samples were taken from outcrops along the SW shore of Commencement Bay and analyzed using X-ray powder defraction (XRD) to determine whether or not the mineral assemblages of each outcrop were of the same origin. The mineral groupings consistent within the sampling area included quartz, muscovite, plagioclase feldspar species (andesine and albite), or potassium feldspar species (sanidine). This implies similar provenance for all outcrops and is consistent with deposition during the same episode of glacial retreat. These data were collected in support of an anisotropy of magnetic susceptibility (AMS) study. Mineral assemblage information coupled with AMS can provide a glimpse of past streamflow conditions within the Olympia beds, suggesting a broadly N-S pattern of streamflow. The combined mineralogical and magnetic results suggest a way forward for mapping streamflow in the Puget Sound region during glacial retreats, eventually leading us toward a better understanding of present-day glacial retreat. 

Giant low surface brightness galaxies (GLSB) are a class of spiral galaxies with larger and fainter disks than typical spirals. Previous theoretical work suggests that their formation history is distinct from that of normal spiral galaxies. Two main theoretical models for GLSB formation have been proposed. One possibility is that they begin as ordinary spirals and undergo a face-on impact with a small satellite, creating a compression wave (i.e., a collisional ring) which excites star formation throughout the neutral hydrogen disk and results in a large, faint stellar disk. A competing possibility is that GLSBs begin as elliptical galaxies or normal spirals and acquire disks through tidal disruption and accretion of a satellite galaxy. Preliminary investigation of these objects has shown that they possess bulges which are morphologically and photometrically similar to typical elliptical galaxies, suggesting that the GLSB disks could be the remnants of a satellite accretion event. Using the Apache Point Observatory, we have obtained longslit spectra of the central bulges of two GLSBs, Malin 2 and UGC 6614. Combining these data with spatially resolved spectra of the disks taken at the McDonald Observatory allows us to compare the disk and bulge kinematics and distinguish between the possible formation scenarios. Our analysis reveals that disk and bulge kinematics are closely correlated in both targets, which is consistent with both possibilities but may favor the collisional ring galaxy scenario.

Burkholderia thailandensis uses acyl homoserine lactones (AHLs) as quorum sensing (QS) signals. Broadly, QS is a communication system that, at high cell densities, allows bacteria to coordinate group activities. Recent work from our lab has shown that in B. thailandensis, QS controls contact dependent growth inhibition (CDI). CDI is an intraspecies bacterial competition system  where CDI-proficient bacteria (CDI+) contain a three-protein system of CdiA, CdiB and CdiI. CdiA is a toxic protein displayed by CdiB, and CdiI neutralizes the toxic activity of CdiA. We predict that QS-control of CDI is a means of eliminating QS mutants from the population. B. thailandensis has three QS-systems; QS-1, QS-2 and QS-3, which each comprise of a specific transcription factor and a cognate AHL signal synthase that produces a specific AHL. A B. thailandensis mutant in all three synthase genes (btaI1-3) is defective at growth, inhibiting a cdiAIB mutant. However, we do not know the specific contribution of each AHL signal synthase. Thus, we sought to test the CDI activity of synthase mutants against cdiAIB mutants within a competition. We compared the starting and ending ratios of the different strains tested in each competition. Preliminary results have demonstrated that the btaI1-3 mutant is CDI defective, relative to wild type. However, signal synthase mutants are not defective at CDI. QS is required for WT levels of CDI. Additionally, we are investigating the dynamics of how CDI controls the growth advantage of QS mutants. A btaR1 mutant has a growth advantage when co-cultured with wild type in liquid but not during growth on a solid surface, which allows for CDI to occur. Thus, we are evaluating if CDI is responsible for restraining the growth advantage of the btaR1 mutant during growth on a solid surface.

Intra-articular calcaneal (heel bone) fractures are common tarsal injuries that can require months for recovery. There are a few different treatment options available for these fractures including nonsurgical immobilization treatments, open reduction and internal fixation (ORIF) and percutaneous fixation. Classification of fractures can be a useful tool for medical professionals for communication and treatment planning. The existing calcaneal fracture classification systems used in clinical settings are subjective and not reliable tools for determining the best treatment for patients especially for highly fragmented (comminuted) calcanei. Calcaneal fracture treatments have high complication rates which compounds the need for a better treatment planning tool. The project goal is to develop a new calcaneal fracture classification system that utilizes CT image data to objectively calculate fracture severity metrics of the calcaneus, namely free bone surface area and the volume of surrounding soft tissue swelling. These metrics will be included on a calcaneal fracture report in addition to a model of the fractured calcaneus with fracture lines indicated. The software is developed using the Visualization ToolKit (VTK)  and the calcaneal model generated based on Simpleware ScanIP segmentation of the CT images. In the future, the software can be used to develop an index for the best treatment option for each fracture classification giving medical professionals a tool for aiding in treatment planning and a means of communicating fracture severity.