Huskey Research Exhibition 2016 Program

The PEN collaboration undertook to measure the pion electronic decay branching ratio with a relative uncertainty consistent with the theoretical predictions of the Standard Model. The detector system included a beam counter, beam tracking, an active degrader and stopping target, Multi-Wire Proportional Chambers, a plastic scintillator for particle identification, and a spherical CsI EM calorimeter for energy readings. GEANT4 Monte Carlo simulation is integral to the analysis as it is used to generate ultra realistic synthetic data for all pion and muon decay channels. The events are are constructed so as to match the beam profiles, momentum distribution, and timings and energy that appear in measurement profiles. Ensuring the placement of individual detector element components at the sub-millimeter level and proper construction of active target waveforms with associated noise, enables us to more fully understand resolutions and calibrations as well as the temporal and geometrical acceptances that occur in the detector system. This ultimately leads to reliable discrimination of background events, thereby improving branching ratio extraction.

Key Words: electro-weak, pion, standard model

Among thousands of discovered extrasolar planets, many of them are dramatically different from the planets in our solar system. Hot Jupiter is a Jupiter-like planet but in a remarkably close orbit to its parent star. It is also the easiest type of exoplanet to detect in both transit method and radial velocity method, so it could be studied in more detail. In this presentation, I'll explain how we can detect the structure of hot Jupiter atmosphere with transmission spectrum, and how we construct an atmosphere model to reproduce the observed H\alpha transmission spectral line.

Key Words: Hot Jupiter atmosphere, transmission spectrum

In three dimensions, when a superconductor is topologically non-trivial and has time reversal (TR) symmetry, it carries massless Majorana fermions on its surface. Their gap-less energy spectrum is robust against any weak-enough single-body perturbation that does not break TR symmetry. But is it robust against any perturbation that preserves (TR) symmetry? What kind of perturbation would gap the Majorana energy spectrum without breaking the TR symmetry of the surface? What would be the properties of the resulting surface? In order to investigate this, we mimic the surface of topological superconductor by constructing a “Coupled Wire Model” in two dimensions. We introduce an explicit many-body perturbation that gaps the Majorana energy spectrum and preserves the TR symmetry. Moreover, we derive the “anyon” content that characterizes the resulting gapped surface. This work shows including many-body interaction gives rise to new kind of symmetry preserving phases on the surface of topological superconductor.

Key Words: Topological superconductor, Majorana fermions, Anyon, condensed matter physics

The human brain is a complex biological system, governed by intricate dynamic interactions occurring at multiple levels of resolution. In the current study, we sought to harness this dynamical complexity to bridge the gap between underlying genetic/epigenetic factors and behavioral outcomes, using the brain as an intermediate endophenotype. More specifically, we probed neural networks known to support social perception in addition to biochemical markers—namely, DNA methylation on the oxytocin receptor gene (OXTR)—thought to mediate social behavior. Healthy young adults underwent resting-state fMRI and provided blood samples for epigenotyping. They additionally completed the Autism-Spectrum Quotient (AQ) to determine how these macroscale-neural and microscale-molecular factors relate to the broad autism phenotype (BAP). For each individual, we then computed both temporal and spectral measures of BOLD variability across the whole brain in a voxelwise fashion. We further derived estimates of dynamic connectivity between anatomically-defined regions of interest, allowing us to quantify nonstationary network states within individuals over time. Finally, using a combination of univariate techniques and Bayesian machine learning methods, we attempted to decode both OXTR methylation and BAP from these spatially-distributed neural dynamics. We show that BOLD variance and dynamic connectivity can jointly predict one’s epigenotype in addition to behavioral phenotype. These findings critically demonstrate that system fluctuations during the “baseline” resting state are far from mere noise. They additionally bolster recent hypotheses regarding the role of oxytocin in autistic spectrum behaviors, suggesting that these traits may result from deficits in oxytocin’s ability to modulate the salience of social information.

Key Words: fMRI, oxytocin, epigenetics, dynamical systems, autism

Rodolfo LLinas, a leading neuroscientist, has argued that the entire evolution of the human brain has been driven by our need for locomotion, the most fundamental form of behavior. By quantifying the brain to muscle interface (the corticospinal system), through the use of stimulus response relationships, researchers are starting to comprehend how the brain functions. Transcranial Magnetic Stimulation (TMS) is rapidly becoming a leading neurological clinical technology over direct electrical stimulation as it avoids pain, has a high degree of localization, and eliminates the uncertainty of whether or not stimulation has occurred. The key indicator of excitability of a specific muscle, due to TMS, is the stimulus intensity versus motor-evoked potential (MEP) recruitment curve. Conventional analysis of the recruitment curve assumes a sigmoidal shape with constant additive Gaussian noise. However, as the MEP responses are very sensitive to intrinsic, visceral, and extrinsic factors, additive noise models do not account for the observed intensity dependent variability. We have developed a new mathematical model that allows for intensity dependent variability about the MEP response and that calculates the cortico-motor threshold (a fundamental neurological concept) within its parameterization. In a comparison to the conventional approach to brain-muscle modeling, (e.g., model fits and parameters relating to the cortico-motor threshold, maximal MEP size, curve slope, and baseline MEP size), we found that our model performed better than the conventional (“gold standard”) approach. By accurately capturing the relationship of recruitment curves, neuroscientists can further understand states of the corticospinal system and subject specific parameters for TMS can be tested quickly and without unnecessary exposure to magnetic stimulation.

Key Words: Motor-evoked potential (MEP), Recruitment curve, Transcranial Magnetic Stimulation (TMS)

The production and assembly of the extracellular matrix (ECM) is a well-regulated process that can lead to congenital disorders, fibrosis, and cancer when perturbed. Through loss- and gain-of-function experiments in Xenopus laevis embryos, we have identified a role for the cadherin-binding protein, plakoglobin (Pkg), in ECM assembly. Our data support the hypothesis that Pkg regulates the expression and assembly of the fibronectin (FN) protein, a major component of the ECM. Embryos deficient for FN or Pkg are unable to assemble FN fibrils. Fibrillogenesis remains perturbed when the FN protein is added back to FN or Pkg knock-down embryos. This indicates that a cell must express the FN protein in order for FN fibrillogenesis to occur. Embryos in which fibrillogenesis is perturbed do not develop properly, resulting in short embryos. These findings identify a previously unappreciated role for Pkg as a regulator of de novo ECM expression and assembly.

Key Words: Extracellular matrix, adhesion, signaling, development

Malnutrition affects 25% of the world’s children under age 5 and is perpetuated in part by a chronic, subclinical inflammatory condition of the gut called environmental enteropathy (EE). EE is difficult to diagnose without intestinal biopsy, and even more difficult to treat, as the condition is not well understood. Regenerating protein 1 (Reg1), a protein known to play a role in inducing tissue regeneration in the pancreas and intestines, has recently been used as a biomarker for studying the breaches in the gut barrier that can occur during EE. There is evidence to suggest that Reg1 is responding to exposure to microbial byproducts that cross the compromised epithelial barrier, but it is unclear whether the resultant increase in Reg1 is protective or pathogenic. I hypothesize that Reg1 plays a protective role in maintaining gut barrier integrity during EE. To test this hypothesis, I will use enteroid cultures (fully differentiated three-dimensional primary intestinal epithelial cells) to determine the microbial signals that induce Reg1, as well as using an EE disease model in mice to resolve the participation of Reg1 in gut damage and regeneration and to determine whether or not Reg1 harbors potential as a therapeutic target to accelerate gut healing during EE.

Key Words: malnutrition, global health, health and human disease, regenerative biology

Mitochondria are organelles that provide energy and regulate life-death decisions in eukaryotic cells. Over time, mitochondria become damaged, rendering them dysfunctional. Damaged mitochondria can lose their ability to generate energy and cause inappropriate cell death. This necessity of properly functioning mitochondria for cellular health underscores the importance of maintaining a healthy pool of mitochondria. One major mechanism of regulating mitochondria quality control is mitophagy—the selective removal of damaged mitochondria from the cell. Impaired mitophagy is associated with a number of pathological conditions, including cancer and neurodegenerative diseases such as Parkinson’s disease. Mitophagy is regulated by different biochemical signaling pathways, including the recently discovered PINK1-Parkin pathway. Upon mitochondrial damage, the protein Parkin translocates from the cytosol to the mitochondria where it is activated by the protein PINK1. Activated Parkin then targets mitochondrial proteins for degradation. However, the precise mechanisms by which Parkin relocalizes to the mitochondria in response to mitochondrial damage remains unclear. I hypothesized that the small GTP-binding protein, RalA, may be involved in recruiting Parkin to mitochondria because it is a possible Parkin-interacting protein1 and RalA can shuttle from the cytoplasm to the mitochondria. My preliminary data supports my hypothesis and indicates that RalA colocalizes with Parkin at damaged mitochondria and cells engineered to express decreased levels of RalA exhibit impaired Parkin recruitment following mitochondrial damage. These data suggest that RalA plays a critical role in mitophagy through regulating Parkin recruitment. Understanding how Parkin is recruited to damaged mitochondria may provide insight into the growing list of diseases associated with impaired mitophagy.

Key Words: mitochondria, mitophagy, RalA, biomedical science

America currently faces an obesity epidemic resulting in increased risk of diabetes, heart disease, and cancer. Although, diet and exercise are the preferred approaches to combat this, most individuals find it difficult to adhere to the diet long-term in part because the diet becomes less efficacious. Why do diets lose their efficacy? We speculate that our evolved ability to adjust to our environment may explain adaptation to diet. The main system responsible for such homeostatic adaptation is the sympathetic nervous (also involved in fight or flight responses). Indeed, the sympathetic nervous system is a master regulator of energy homeostasis and is employed under times of high energy need, such as activity and fasting. Therefore, we sought to determine how the sympathetic nervous system controls fat loss and whether it changes activity as a function of time on diet. We have found during the early phase of dietary weight loss, the sympathetic nervous system signals to breakdown visceral fat (ie belly fat). After twelve days, when the diet becomes less effective, we observed that the sympathetic nervous system activity is dramatically decreased thereby dampening its ability to cause fat breakdown. Beyond this observation, we’ve found that abnormally activating or inhibiting sympathetic activity to fat causes improved or abolished fat breakdown which is suggestive of potential weight loss therapies.

Key Words: diet efficacy, fat loss, sympathetic nervous system

There is a positive correlation between the accumulation of tumor infiltrating lymphocytes (TIL) in tumors and favorable clinical outcomes. However, TIL fail to eradicate tumor cells and prevent disease progression. While their failures have been attributed to their exhaustion (poor proliferation and cytokine production), the underlying molecular basis of this state is not fully understood. Generally, T cell activation induces massive clonal expansion, which requires robust duplication of proteins, lipids, and nucleic acids, which in turn requires rapid generation of cellular building blocks and energy. Activated T cells induce cellular signals that promote metabolic reprogramming to meet these increased bioenergetic and biosynthetic demands. This notion is supported by studies that have shown that glucose uptake and its metabolism via aerobic glycolysis (Warburg effect) are essential for generation and activity of effector T cells. Whether this essential metabolic reprogramming happens in TIL or not is unknown. Our studies have shown that TIL metabolically less active than acute effector CD8 effector T cells (CD8 Teff). However, TIL use glycolytic metabolism more than age-matched CD8 Teff do while they use similar level of oxidative phosphorylation metabolism (OXPHOS). These results suggest that TIL have metabolic profile that is distinct from acute and late CD8 Teff. Our investigation of glycolytic markers revealed that TIL express more PKM2 and take up more glucose than age-matched CD8 Teff. The amount of glucose that TIL take up is similar to that of acute CD8 Teff, which express significantly higher level of glucose transporters (Glut1). These results suggest that TIL have glycolytic defect downstream of glucose uptake. In line with this, we have observed significant enhancement in TIL metabolic activity when we bypassed glycolysis by providing pyruvate. We did not observe deficiency in the expression of components of the PI3K/PDK1/Akt/mTOR/HIF1a signaling pathway (which has been reported to promote aerobic glycolysis) in TIL. In conclusion, glycolytic metabolism is suppressed in TIL although they express glycolytic machinery at similar level as acute CD8 Teff, which are highly glycolytic. Future studies will determine mechanism underlying TIL metabolic deficiency and if promoting aerobic glycolysis in TIL can restore their proliferation and effector function

Key Words: Antitumor, immunology, metabolism, regulation, glucose

In nature, resources are limiting. Organisms must therefore allocate them strategically to grow into reproductive adults. However, at the molecular level, little is known about how organisms allocate resources to body maintenance or the production of progeny. I used genome-level reverse genetics in the nematode Caenorhabditis elegans to gain molecular understanding of the trade-off between soma and egg production. Normally adult C. elegans store energy in the form of fat in the adult soma and the developing eggs/embryos. I found 21 genes that when knocked-down lead to fat being accumulated only in the eggs/embryos, but not in the body of the worms. We named this phenotype eof (Egg Only Fat). Through molecular and cell biological approaches, I am now defining how the eof genes normally allocate nutrients to the soma. Some eof genes are conserved in different species, including human, suggesting that the mechanisms controlling soma-reproduction nutrient allocation could be evolutionary conserved. Analysis of the eof mutant worms will advance our understanding of the ancient mechanisms directing resources either to body maintenance or to reproduction, a critical decision for the survival of a species.

Key Words: fat, metabolism, C.elegans, reproduction

Ischemia-reperfusion (IRI) injury in skeletal muscle is a common complication in many diseases and clinical settings that leads to loss of muscle mass and function. Unfortunately, there are currently no preemptive treatments to reduce IRI in skeletal muscle. Generation of mitochondrial reactive oxygen species (ROS) during reperfusion has been identified as a major mediator of IR injury. We hypothesized that reversible suppression of mitochondrial respiration by covalently linking nitric oxide moieties to protein thiols (S-nitrosylation), which is known to inhibit enzyme activities, may mitigate IR injury to skeletal muscle. We subjected mice to 1hr of unilateral ischemia by application of a rubber-band tourniquet or to a sham procedure (Con). Five minutes prior to tourniquet removal, we performed intramuscular injection of a ubiquitous s-nitrosothiol (GSNO), a mitochondrial-specific antioxidant (MitoNAP). a mitochondria-specific s-nitrosothiol (MitoSNO1), or vehicle control (IR). We assessed maximal muscle force production 14d following injury and found IR, GSNO, and MitoNAP groups generated significantly less maximal force compared to Con (~50%). However, the MitoSNO1 group had no loss in maximal force. We then assessed gastrocnemius muscle mass and found a significant reduction in IR, GSNO, and MitoNAP groups (~40%) compared to control. MitoSNO1 treated animals had no loss in muscle mass. Taken together, targeted S-nitrosylation of mitochondrial proteins profoundly protects skeletal muscle against IR injury-induced loss in muscle mass and function. Therefore, mitochondria targeted interventions may provide an efficacious means for protection of skeletal muscle against IR injury.

Key Words: Ishcemia-reperfusion, protection, mitochondria, skeletal-muscle

I present an analysis of ionization mechanisms in a sample of 65 luminous infrared galaxies as traced by their near-infrared line emission. These galaxies are hotbeds of extreme merger-driven star formation and are sometimes observed to contain actively accreting black holes. Both phenomena are obscured by dust within the galaxies, necessitating the need for long-wavelength data to assess the nature of their activity. My near-infrared spectra are characterized by strong emission from hydrogen recombination lines, [Fe II] emission, and lines of heated molecular hydrogen. The emission line ratios overwhelmingly favor ionization via radiative shocks over photoionization by the starburst. In addition, no evidence of embedded black hole accretion (as traced via broad emission lines or high ionization emission lines) is observed in LIRGs with star-formation-like optical spectra. This study is part of the Great Observatories All-Sky LIRG Survey (GOALS).

Key Words: Galaxies, Mergers, Starbrust

Histamine is a neurotransmitter necessary for vision and visual processing in Drosophila melanogaster. Histamine is rendered inactive by metabolism to carcinine, which can then be metabolized back to produce active histamine. Direct detection of both histamine and carcinine in single Drosophila brains has not been previously reported, likely due to the low abundance of these neurotransmitters. Using capillary electrophoresis coupled to fast scan cyclic voltammetry (CE-FSCV), we quantify the amount of histamine and carcinine in a variety of tissues obtained from single flies. Limits of detection were low, 4 ± 1 pg for histamine and 10 ± 4 pg for carcinine, and both analytes were detected in the eyes, brain, and cuticle of Drosophila. Tissue content of histamine and carcinine in all of these tissues was determined in a wild type fly (Canton S) and in two mutant strains (tan3 and ebony1). In these mutants, normal metabolism of histamine and carcinine is disrupted: tan3 flies cannot metabolize carcinine back to histamine and ebony1 flies cannot metabolize histamine into carcinine. Comparisons of tissue content of histamine and carcinine in these flies to wild type tissue content showed that tan3 flies had significantly higher carcinine content in their eyes and brains than other strains tested. Unexpectedly, histamine content did not significantly differ across strains. Dopamine and N-β-alanyl-dopamine, a metabolite of dopamine produced by the same enzyme that metabolizes histamine to carcinine, are also quantified in Drosophila tissues.

Key Words: D. melanogaster, capillary electrophoresis, electrochemistry, neurotransmitter

I will discuss a recent measurement of a light wavelength at which the ac electric polarizability equals zero for Rb87 atoms, known as a "tune-out" wavelength, as well as progress on measurements of the vector polarizability near this "tune-out" wavelength. Measurements of tune-out wavelengths and the vector polarizability between multiple lines allows separation of individual contributions to the polarizability from higher-lying states and the core up to ratios of matrix elements. Accurate knowledge of these ratios should serve useful as a theoretical benchmark and in atomic parity violation experiments.

Key Words: physics, atoms, light

Patients in intensive care units (ICUs) are susceptible to subacute, potentially catastrophic illnesses such as sepsis, hemorrhage, and respiratory failure. Early detection should improve outcomes, but even subtle clinical signs may only manifest late in the course. These signs – signature patterns in the dynamics of heart rate, respiratory rate, blood pressure, and oxygen saturation – may be present much earlier, but at amplitudes below the threshold of clinical detection. We hypothesized that predictive analytics might allow us to identify such signatures using large-scale time series analyses. We analyzed 144.2 patient-years of physiological monitoring time series from 9,199 consecutive admissions to neonatal, medical, and surgical ICUs at our tertiary care academic hospital (601 infants and 8,598 adults). We performed multivariable statistical analyses of mathematical time series measures from linear and non-linear domains. Clinicians identified 1,248 episodes of hemorrhage, respiratory failure, or severe sepsis from standardized review of individual charts. The incidence rates ranged from 5.2 to 25 per 100 admissions. In adults, the impact of adverse events increased the ICU length of stay by a median of 2.4 to 14.0 days and increased in-hospital mortality by 2.4 to 4.2 fold over patients who did not suffer such events. Multivariate models using physiologic monitoring parameters and ECG-derived calculations to predict illnesses up to 24 hours before clinical detection and intervention had bootstrap-validated C-statistics of 0.61 to 0.78. Physiologic signatures of neonatal illnesses were concordant amongst themselves but discordant with all adult illnesses. Signatures of hemorrhage and respiratory failure leading to unplanned intubations were distinct and were concordant across adult ICUs. Severe sepsis in the adult ICUs, however, had discordant physiologic signatures. We conclude that subacute, potentially catastrophic illnesses have physiologic signatures that are detectable in the hours preceding clinical detection and intervention.

Key Words: physiology, critical care, big data, hemorrhage, sepsis, respiratory failure

Octopamine is an endogenous biogenic amine that plays important roles as a neurotransmitter, neurohormone, and neuromodulator in invertebrates, and has functional analogy with norepinephrine in vertebrates. Fast scan cyclic voltammetry (FSCV) is an excellent technique to detect the rapidly changing levels of octopamine in the brain, however, an FSCV waveform has not been optimized for octopamine detection in situ. The FSCV waveform was optimized so that the potential for octopamine oxidation would not be near the switching potential and that the secondary peak would be observed, which is important to consistently detect and quantify octopamine. Endogenous octopamine release was stimulated with two new stimulation methods, the ATP sensitive channel P2X2, and a red-light sensitive channelrhodopsin CsChrimson. For CsChrimson mediated release, the evoked current decreases in the presence of octopamine synthesis inhibitor, disulfiram, which confirms that the current is due to octopamine and not its precursor, tyramine. On average, a 2 s stimulation with CsChrimson evokes 0.15 ± 0.07 µM of octopamine release in the larval VNC. Current due to evoked octopamine is stable upon repeated stimulation with 2 and 5 minutes interstimulation times, and the release is dependent on the frequency of applied light pulse. The ability to study this important neurotransmitter in Drosophila will allow studying the effects of drugs and mutations on octopamine release.

Key Words: Electrochemistry, Neuroscience, Optogenetics, Drosophila

After Fermi launched in 2008, it has revolutionized gamma-ray pulsar astronomy, by enabling the discovery of many new millisecond pulsars (MSPs). The Fermi Pulsar Search Consortium (PSC) has organized hundreds of radio observations of pulsar-like Large Area Telescope (LAT) unassociated gamma-ray sources. In less than 3 years, the PSC has discovered 44 new MSPs. These new discoveries number more than all MSPs in the first 20 years (from 1982 to 2002) of MSP searching combined. Notably, among the 44 new MSPs, there are at least 10 “black widows” and 4 “redbacks” (the rare populations of eclipsing pulsar binaries). As one of the PSC radio telescopes, the Green Bank Telescope (GBT) has, outstandingly, helped uncover 25 new MSPs. Here we report the properties and timing analysis of the 2 MSPs most recently discovered with the GBT: PSR J0621+25 and PSR J2042+02. By searching more Fermi unassociated sources from the LAT 1-year, 2-year and soon 3-year Point Source Catalog, the GBT will almost certainly discover additional MSPs. The newly discovered MSPs will provide more potential additions to the pulsar timing arrays (like NANOGrav) as well as improve the understanding of MSP formation and evolution.

Key Words: pulsars, Fermi, discovery, Green Bank Telescope, Gravitational waves

Top-down protein analysis preserves combinatorial post-translational modification (PTM) information, but is complicated by the distribution of a protein’s signal into many charge states. In a complex sample, less abundant proteoforms cannot be easily resolved from more abundant overlapping species in MS1 spectra. Ion-Ion Proton Transfer (IIPT) will reduce analyte charge and separate overlapping signals, but uncontrolled charge reduction results in products with m/z values extending beyond available scan ranges. Parallel ion parking was developed by McLuckey et al. to control ion-ion reaction kinetics. Here we report progress toward enabling IIPT coupled with parallel ion parking on an Orbitrap Elite. We demonstrate its utility in the analysis of intact ribosomal proteins purified from HepG2 cells and more complex biological protein mixtures. The realized signal-to-noise ratio of parked ions was increased by up to two orders of magnitude, which allowed for the observation of low level proteoforms that were indiscernible in the MS1 spectrum. In addition to an increase in signal intensity attributed to each species, consolidating all ion current into a single charge state simplifies data-dependent selection of precursor ions. ETD and HCD MS3 analyses were performed on the parked products and a combination of fragment and intact mass data was used to identify 33 of 81 ribosomal proteins expected in the mixture, ranging in mass from 3 to 35 kDa. Of these, 10 contained post-translational modifications. These identifications were the result of a single LC-MS run.

Key Words: Proteomics, Mass Spectrometry, Ribosomes

Heart failure is the leading cause of death. Increased beta-adrenergic (βA) signaling contributes to heart failure through simultaneous yet differential regulation of hypertrophy and apoptosis in myocardial tissue. These combined responses result in pathologic hypertrophy preceding heart failure. Understanding how βA signaling differentially regulates the hypertrophic and apoptotic signaling networks may yield new therapeutic targets for treatment of heart failure and also yield insight into the mechanism of differential regulation of multiple phenotypes by a single stimulus. I use a combination of computational modeling and experimental approaches to investigate the heterogeneous cell decision-making process between hypertrophy and apoptosis. Collectively, these studies are both hypothesis-testing and hypothesis-generating and I expect these studies to identify and validate new pharmacological targets for the improved treatment of heart failure.

Key Words: heart failure, computational modeling, systems biology

Chemokines are a class of molecules known for their chemoattractant properties within the adaptive immune system, but have also been shown to possess antimicrobial activity against a wide range of bacterial pathogens. The mechanism(s) by which these chemokines kill bacteria is not well understood. Our current study indicates that the interferon-inducible, ELR(-) chemokine CXCL10 kills the Gram-positive pathogen Bacillus anthracis through multiple molecular mechanisms. One mechanism is mediated by interaction of CXCL10 with the bacterial membrane complex, FtsE/X, and does not require the presence of the CXCL10 C-terminal α-helix. The second mechanism is FtsE/X receptor-independent and kills through general membrane disruption due to the C-terminal α-helix. This study represents a new paradigm for understanding how chemokines exert an antimicrobial effect that may prove applicable to other bacterial species and result in the development of novel therapeutics to treat infections.

Key Words: Bacillus anthracis, antimicrobial mechanism, chemokine

Entamoeba histolytica is an enteric parasite that causes diarrhea. E. histolytica adheres to host cells by the Gal/GalNAc lectin and disrupts the mucosal barrier, penetrates underlying tissue and destroys cells. Host responses at the site of infection are critical for resistance, thus the mucosal response against E. histolytica infection is a significant contributor to immunity. Intestinal epithelial cells (IECs) serve as effectors of the mucosal immune system and produce inflammatory mediators including IL-1β during amebiasis. IL-1β is known to suppress the production of IL-25 and is increased during E.histolytica infection, which is also produced by IECs. IL-25 is suppressed during E. histolytica infection in human and mouse model. We hypothesize that during E. histolytica infection IL-25 has a protective role, and to test this hypothesis we intraperitonealy administrated rIL-25 in CBA mice. We found that rIL-25 treated mice had a significantly lower infection rate, as shown through culture, ELISA and E. histolytica specific QPCR. Histologically, there was significantly less epithelial disruption in rIL-25 treated mice. Therefore we have concluded IL-25 plays a protective role during amebiasis. It is interesting to know how IL-25 plays its protective role. We have found that patients with amebic colitis express higher TNFα, and rIL-25 can suppress TNFα in E. histolytica challenged mice. Therefore we hypothesized IL-25 could play a protective role by suppressing pathogenic TNFα during E. histolytica infection. This work will inform our knowledge on the role of IL-25 in the mucosal defense against amebic infection, ultimately improving treatment and vaccine strategies.

Key Words: Amebiasis, mucosal response, IL-25

Neisseria gonorrhoeae, or the gonococcus (Gc), causes the sexually transmitted infection gonorrhea. The hallmark of gonorrheal disease is characterized by the large influx of immune cells, namely neutrophils, to the site of infection. Neutrophils are specialized cells that have an arsenal of mechanisms to kill bacteria; however, a population of Gc can survive the killing activities of neutrophils. We have found that Gc uses two cell wall-acting enzymes, called lytic transglycosylases (LTs), to mediate survival from neutrophils. The known function of LTs is to break down the bacterial cell wall in a regulated fashion, consequently releasing cell wall fragments that have the potential to modulate immune cell function. We did not find a role for the release of cell wall fragments in mediating survival from neutrophils. Instead, we found two reasons to explain how LTs protect Gc from neutrophil killing. First, LTs protect Gc from killing by the neutrophil antimicrobial protein lysozyme. Lysozyme kills bacteria by degrading the cell wall, but bacteria like Gc are enveloped in a membrane that surrounds the cell wall, effectively occluding lysozyme from access to the cell wall. We found that LTs are important for maintaining the integrity of this envelope. Second, we also found that LTs are important for restraining the killing activities of neutrophils. We hypothesize that LTs limit the amount of bacterial-derived signals that can be recognized by neutrophils to enhance neutrophil killing responses.

Key Words: Neisseria gonorrhoeae, immune cells, lysozyme, cell wall

It remains unclear how history of antibiotic exposure affects subsequent resistance evolution trajectories in sequential therapies. Knowledge of potential evolutionary paths of resistance given prior history of drug exposure can help clinicians prescribe regimens that minimize resistance levels. We studied how history of past drug exposure affects the development of resistance during subsequent drug therapy in Pseudomonas aeruginosa. We serially passaged replicates of P. aeruginosa to increasing concentrations of piperacillin, tobramycin and ciprofloxacin daily for 20 days. These single-drug resistant mutants were then passaged to the other drugs for 20 days, resulting in six sets of mutants evolved to two drugs each. Minimum inhibitory concentrations (MICs) of all drugs were measured for all lineages during the adaptive evolution. We observed drug sequence specific effects where: adaptation to the first drug limits subsequent adaptation to the second drug (e.g. past piperacillin adaptation limits subsequent development of tobramycin resistance), adaptation to the second drug decreases the resistance to the first drug (e.g. evolution to ciprofloxacin after piperacillin and tobramycin result in loss of piperacillin and tobramycin resistance, respectively), or final resistance levels depend on the order of the sequence (e.g. piperacillin resistance is less when evolved to piperacillin then ciprofloxacin compared to the reverse). These effects show how adaptation history to antibiotics can complicate strategies for mitigating resistance of bacterial pathogens. Effective antibiotic stewardship must account for these effects in the development of antibiotic resistance in order to deter the onset of the post-antibiotic era.

Key Words: antibiotic resistance, evolution, hysteresis

Black youth are more likely to be arrested, detained, prosecuted, incarcerated or transferred to the adult criminal system compared to White youth (Puzzanchera, Adams, & Hockenberry, 2012). Previous research on disproportionate minority contact has focused primarily on law enforcement contact, arrest and sentencing; only limited progress has been made in examining disproportionality after sentencing. Our study addresses this gap by examining disproportionality within the context of juvenile probation violations by: 1) examining racial disproportionality in the number of probation violations among juveniles, and 2) exploring contextual factors that may drive trends in juvenile probation violations numbers.

Key Words: law, psychology, race, youth

Objectives: The purpose of this study was to determine predictors of adolescent smoking outcomes including receptivity to tobacco marketing, lifetime smoking, and current smoking in South Korea. Methods: This study used a cross-sectional descriptive correlational design. The survey was conducted with 13- to 15-year-old adolescents (n = 740) attending middle schools in Seoul, South Korea. Addresses of licensed tobacco retailers (n = 3,488) were obtained from borough offices of Seoul. Geographic Information Systems were used to measure factors related to licensed tobacco retailers and multilevel modeling was used to determine predictors of adolescent smoking outcomes. Results: Predictors of receptivity to tobacco marketing were peer smoking and number of licensed tobacco retailers passed. Predictors of lifetime smoking were gender, perceived economy, weekly allowance, sibling smoking, peer smoking, and number of licensed tobacco retailers passed. Predictors of current smoking were gender, weekly allowance, sibling smoking, and peer smoking. Conclusions: Predictors found in this study need to be considered in adolescent tobacco prevention programs and policies.

Key Words: adolescent, smoking, multilevel analysis, geographic information systems

In recent years (2008-2010), large reductions were noted in traffic casualties in Virginia. For example, in 2008, traffic fatalities dropped to the lowest level since 1961 and annual reduction of 205 fatalities was unprecedented. Although characteristics of traffic crashes are believed to have changed, it is unclear what might be contributing to these changes. This study was to identify factors associated with the recent changes and collected socio-demographic-economic data and vehicle and driver registration data in quarterly and yearly formats. It employed several statistical techniques such as a principle component regression to cope with multicollinearity often found in these data. The study concludes that funds for highway safety improvement contribute to improving traffic safety and economic conditions are a crucial factor for examining traffic safety. A young age group has a great influence on overall traffic safety conditions.

Key Words: Traffic Safety, Economic Recession, Regression Analysis

Adolescents who date older romantic partners are at risk for a variety of negative outcomes, including teen pregnancy, STIs, unwanted sexual activity, delinquency, and suicide attempts (e.g., Young and D’Arcy, 2005). Thus, statutory rape laws are designed to prevent risky sexual relationships between adolescents and older partners. However, we do not know whether teens are even aware of the laws—a prerequisite to assessing how much the current legal framework actually shapes teens’ behavior. We queried 210 youth (M = 16.9 years) at-risk for dating older partners about their knowledge of actual statutory rape laws in their state. Overall, teens answered 71.1% of items correctly, although knowledge varied widely according to the participant age and age gap in question. Participants showed particularly poor knowledge in two situations: (1) illegal sex when both partners are under age 18, and (2) illegal sex between a teen 18+ and a minor partner just one or two years younger. GEE analyses revealed that older teens answered more accurately than younger teens (Wald χ2 (5, N = 1680) = 104.727, p < .001), although evidence suggests this is because laws are simpler and more intuitive for older teens, not because older teens are more informed than younger teens. Results suggest that prevention and educational efforts (traditionally targeted at young adults) need to be extended downward to the youngest teens, given that younger teens had the worst knowledge and can be considered both victims and perpetrators under statutory rape laws.

Key Words: adolescents, at-risk, legal knowledge, age gaps, statutory rape

Not only do scripture-reading practices matter, but they help shape the values, character, and daily life of the communities that engage in them. These effects do not remain within the bounds of community, but often have far-reaching consequences in larger society. The following presentation will briefly illustrate the scriptural-reading practices of John Perkins, an African-American Evangelical civil rights activist who was a founding member of the Christian Community Development Association and Jerry Falwell, a White Southern Baptist televangelist and founder of Liberty University in Lynchburg, Virginia. Both organizations--the Christian Community Development Association and Liberty University--were born out of appeals--albeit very different appeals--to scripture. Through the examination of these appeals we get a glimpse into the soul of these institutions, and the role scripture has played in their formation and work in the world.

Key Words: scripture, Lived Theology, John Perkins, Jerry Falwell

Kamala Khan is a new kind of superhero. She is Marvel’s first Muslim-American superhero to hold her own title as Ms. Marvel and the Ms. Marvel series has succeeded despite Kamala being, by almost every definition of the word, a minority figure: female, teenaged, Pakistani-American, and Muslim. In most of these ways she is different from her superheroic predecessors; however, her association with an Abrahamic faith aligns her with characters like DC’s Superman and Marvel’s Spider-Man. Superman and Spider-Man are icons in American myth and embody, for many, religious narratives from the Judeo-Christian tradition. Observing the history of the American tradition of superhero comics, starting in the 1930s and continuing up until the present, this research addresses the ways in which Kamala Khan fits within this canon of American popular myth and the ways in which she deviates from the norm. Focusing on Kamala Khan’s origin story, this research hopes to answer the question of how the medium of comics can be used to incorporate the Islamic tradition and culture into American popular culture. Kamala Khan is not just a new kind of superhero; she is also a new kind of American mythic icon: an archetype for a Muslim-American in a post-9/11 America.

Key Words: Islam, comics, myth

I will represent my research of the reassessment of the artistic features and religious significances of a group of Buddha images, which feature the depiction of the Buddhist cosmology on the bodies of the Buddha. Extant cases were found throughout the historical sites where Buddhism once flourished along the ancient trade route interconnecting India, Central Asia, China, and Japan. They have been thoroughly studied since 1930s, however, a series of aspects yet remain unclear. The excavations in the 1990s of a series of Buddha statues have brought this topic back into focus. After approaching the imagery by reexamining the transmitting route of the essential motifs shown in the imagery, I argue that those examples are not in consistency and should be re-categorized according to their variations. Meanwhile, the transmission routes brought up by previous scholars requires updating. This study thus sheds light on interpreting the artistic value of the Shandong statues excavated recently. A question I put forward is whether the dissimilarity expressed in many aspects among all the examples imply that multiple categories should be applied to name the images. Naming and classification are never the fundamental objectives of studying art works, whereas patterns and assumptions are never the obstacles of admitting the individuality of each single work.

Key Words: Buddhist art, transmission, silk route

What does it mean to be an empowered Tibetan Buddhist nun in the 21st century? How do contemporary debates on feminism, Buddhism, and monasticism in the West inform this definition of empowerment, and how is it influenced by Tibetans’ mass migration and exile in India? My presentation will answer these questions through an analysis of the Tibetan Nuns Project (TNP), which was founded in 1987 to provide a base for nuns who escaped following the destruction of their nunneries after the People’s Liberation Army’s advance into Tibet (1950), and the Cultural Revolution (1966-1976). I approach Tibetan exile beyond the prism of forced dislocation and loss, and argue that migration to India paradoxically gave unprecedented religious freedom to nuns. This led to pedagogical innovations in nunneries, and became an opportunity to “leave behind the rubbish” of gender-based discrimination (Rinchen Khando Choegyal, TNP Founder and Director, 2013). I analyze how the freedom to establish monastic institutions in exile necessitated a translation of “Tibetan culture” for patrons and potential sponsors of the putative “Tibetan cause” in Europe and North America, who are TNP’s largest supporters. I focus on TNP initiatives such as the newly instituted doctoral program, the Jang Gonchoe debating festival, and the debates around full ordination, all of which had previously been reserved for male monastics. My sources include archival materials from the Indian and Tibetan governments; scriptural and exegetical materials, such as monastic curricula and doctrinal texts; and interviews with nuns, teachers, and administrators in nunneries across India.

Key Words: Forced Migration, Tibetan Buddhism, Non-Western Feminisms

Medieval drama is pervasively antisemitic. Yet it is also populated largely by Jewish characters, and sometimes these characters seem to evoke sympathy, particularly at moments of extreme suffering. Do these plays intend their audiences to “see” the suffering of Jews? And what kind of reaction is this meant to elicit? In this talk I will focus on a twelfth-century Latin play, the Slaughter of the Innocents from Fleury. This drama portrays one of the most horrific instances of innocent suffering in the Bible; not incidentally, the suffering Innocents are Jews. Medieval theology tended to employ figurative interpretation to replace the story’s literal level—that is, Jewish suffering—with a narrative about Christian martyrdom. I argue, however, that the Fleury play uses biblical interpretation in a different and uniquely dramatic way. In the character of Rachel, the matriarch who “weeps for her children,” this play explores a dimension of literal meaning that allows a suffering Jewish character to be heard. Through this unconsoling literalism, the Fleury Slaughter of the Innocents reveals a space within medieval drama for the counternarrative of Jewish experience at its most and least accessible—in the form of suffering.

Key Words: Drama, Judaism, Bible, Interpretation, Medieval

This paper argues that German Lutheran theologian and anti-Nazi Dietrich Bonhoeffer was influenced by a largely American-based religious movement that scholar Patricia Appelbaum calls “protestant pacifist culture.” In particular it suggests that Bonhoeffer’s later theological education at Union Theological Seminary in New York City caused him to sympathize with many of the positions on pacifism and Christian social ethics that were held by the students and faculty there. In his subsequent struggles against the Third Reich, Bonhoeffer adopted many of the nonviolent ideals of the American Protestant pacifists, and used them to create a community in Germany determined to resist Nazism. Past biographers of Bonhoeffer such as Eric Metaxas and Charles Marsh have tried to ascribe to Bonhoeffer to a single coherent theological position, arguing that he was a born-again evangelical or a neo-Orthodox Barthian. The influence of Protestant pacifist culture on Bonhoeffer’s thought, however, indicates that he drew from a medley of disparate religious influences. This paper suggests that as we restore the full range of influences to our understanding of Bonhoeffer's theology, we deepen our understanding of religion and pacifism.

Key Words: Dietrich Bonhoeffer, Pacifism, Liberal Theology, Nazis, World War II

There are no published genetically informed studies examining the relationship between single motherhood and depression. Traditional research has documented an association between the two, but there are many possible non-causal confounds of this association, including a shared genetic background, or a shared influence by the same socioeconomic factors. This study uses the twin design to examine the causality of the relation between single parenthood and depression. Additionally, although public policy measures have been put in place to support single mothers, they differ significantly even among first world countries, so it is important to investigate whether these policies make a difference in the mental health of single mothers. This study will conduct a cross-cultural comparison using two twin datasets from developed countries with different policies.

Key Words: behavior genetics, twins, single motherhood, depression

Children have a very strong preference for resources to be distributed equally. In the study here, we asked whether they would recognize that inequality is permissible if someone chooses to take less than their fair share. Six-year-olds (n = 16), 8-year-olds (n = 16), and adults (n = 16) watched a series of cartoons involving two characters and four pieces of candy. On half of trials, one character expressed a desire for three pieces and took three, and the other character took the remaining one. On the other half of the trials, one character expressed a desire for only one piece and took only one, and the other character took the remaining three. Participants decided whether each distribution was “okay” or “not okay.” Participants at all ages overwhelmingly said the first type of distribution (where the first character took three candies, leaving just one for the second character) was “not okay.” Interestingly, most 6-year-olds and half of the 8-year-olds also said that the second type of distribution (where the first character actively chose to take just one candy, leaving three for the second character) was “not okay.” All of the adults said this unequal distribution as a result of an active choice was “okay.” An understanding that equal access to resources is more important than an equal distribution of those resources seems to develop sometime within middle childhood. Future research will explore why 6-year-olds fail to distinguish between equal and unequal access.

Key Words: fairness, resource access, child development

Despite people’s stated intentions to spend more time on their most valued goals, they often prioritize based on urgency rather than importance. Using experience sampling in academic and workplace contexts, we examined the frequency of important goal prioritization and identified reliable predictors and consequences of these choices. We find that participants high on polychronicity, who report favorable attitudes toward multitasking, spent more of their time focused only on the activities they valued the most. At the end of the sampling week, more time spent on one’s most valued goals predicted a greater sense of purpose. We propose that comfort with incomplete goals, as assessed by polychronicity, allows people to resist distracting opportunities and instead focus attention on their most valued goals. A better understanding of how polychronicity affects goal prioritization could help people achieve their preferred balance of important and urgent goals and boost wellbeing in turn.

Key Words: multitasking, goal pursuit, goal prioritization

Objectives. To assess the relations between 11 aspects of social support and five cognitive abilities (vocabulary, reasoning, spatial visualization, memory, and speed of processing) and to determine whether these relations between social support and cognition are moderated by age or sex. Method. A sample of 2,613 individuals between the ages of 18 and 99 years completed a battery of cognitive tests and a questionnaire assessing aspects of social support. A measure of general intelligence was computed using principal compo- nents analysis. Multiple regressions were used to evaluate whether each aspect of support and/or its interactions with age or sex predicted each cognitive ability and g. Results. Several aspects of social support were significantly related to all five cognitive abilities and to g. When g was included as a predictor, there were few relations with specific cognitive abilities. Age and sex did not moderate any of the relations. Discussion. These results suggest that contact with family and friends, emotional and informational support, anticipated support, and negative interactions are related to cognition, whereas satisfaction with and tangible support were not. In addition, these aspects of support were primarily related to g, with the exception of family contact. Social support– cognition relations are comparable across the life span and the sexes.

Key Words: ge differences—Cognitive abilities—Sex differences—Social support

Prior work has demonstrated that residential mobility (the act of changing one’s residence) induces anxiety, loneliness, and stress. Interestingly, all three of these variables have been linked to self-control ability, but the relationship between mobility and self-control has not been explored. For instance, feeling loneliness and social exclusion have been shown to impair self-regulation, yet anxiety has been shown to bolster self-regulation in some cases. Probing these competing predictions, we tested the relationship between residential mobility and self-control in two studies. In Study 1, participants were primed to be in a mobile or stable mindset (or control condition) and subsequently completed the Stroop Task, a classic task used to assess self-control. Results showed that mobile-prime participants showed better overall Stroop performance, relative to the other two conditions. In Study 2, we replicated and extended our findings at the neural level of analysis, focusing on the Error-Related Negativity (ERN), an ERP component that has been linked to vigilance and motivation upon monitoring error commission. Participants were again primed to be in a mobile or stable mindset and completed a Go-No-Go Task, while electroencephalography (EEG) was recorded. Results showed that mobile-prime participants made fewer errors on the Go-No-Go, relative to stable-prime participants, and demonstrated higher ERN amplitudes, reflecting increased error vigilance. The results show that, at least in the short run, an anticipated move heightens self-regulation. However, as cognitive resources are limited, over time such vigilance may lead to fatigue and long-term deficits in self-control.

Key Words: Residential mobility, self-control, vigilance, error-related negativity (ERN), cognitive depletion

Many competitions do not occur between mere strangers, but between rivals with a shared history. We examine how rivalry influences the self-regulatory strategies people use during goal pursuit. We demonstrate that prompting people to think about rivals (vs. mere competitors) causes them to view current competitions as more connected to past ones, to be more concerned with long-term legacy, and to pursue personal goals in a more eager, less cautious manner. In Experiment 1, individuals thinking about personal rivalries or incidental competitions indicated that the rival contests felt more connected to past and future competitions. This perception of “embeddedness” was associated with increased legacy concerns. The final two experiments demonstrated that merely thinking about rivalry increased the use of eager self-regulatory strategies. In Experiment 2, serious fantasy sports players who had thought about rivals (vs. nonrivals) used more spontaneous, rather than deliberative, reasoning on the Cognitive Reflection Test (CRT), thereby increasing the number of errors. In Experiment 3, recreational athletes thinking about rivals (vs. non-rivals) immediately began, instead of delayed, goal pursuit. Specifically, thinking about rivals increased the likelihood of skipping an optional practice round before completing a one-shot test. We conclude that rivalries increase the use of eager self-regulation strategies during goal pursuit and that these effects are due to the legacy concerns evoked from the embedded, competitive narrative unique to rivalry.

Key Words: rivalry, competition, motivation, self-regulation, goals

Despite 75% of individuals preferring psychotherapy to prescription medications for anxiety and depression, in 2014, 52% of Americans were on prescription medications for emotional disorders and 13% received outpatient psychotherapy. Although there are many barriers for individuals entering into therapy (e.g., stigma, access to professionals, financial restrictions), it is unknown how individuals automatically conceptualize mental health treatments and their efficacy, which may be an important predictor of services people choose. The current study examines whether individuals’ implicit associations between therapy vs. medication as being effective vs. unhelpful are able to predict whether someone has been in therapy or has used prescription medications for emotional disorders. Volunteers to an online Therapy study (N=12033) completed an Implicit Association Test measuring automatic associations between therapy vs. medications as effective vs. unhelpful, an explicit attitudes measure about the relative efficacy of treatments, and questions about mental heath services utilization. Overall, individuals more strongly associated therapy vs. medications as being effective, both implicitly and explicitly. A hierarchical logistic regression revealed implicit therapy+effective associations predict whether an individual has been in therapy (n=1518) or has taken a psychotropic medication (n=556) beyond individuals’ explicit reports of therapy’s relative effectiveness. Moreover, stronger explicit and implicit therapy+effective associations were associated with greater odds of having been in therapy (vs. taking prescription medications). These results suggest that mental health services utilization is uniquely predicted by how strongly individuals automatically associate the service with being efficacious. Implicit attitudes may be another barrier to individuals seeking therapy that could be addressed when understanding how individuals choose mental health services.

Key Words: treatment attitudes, psychotherapy, treatment utilization

Historian Amy Thompson McCandless has called the nineteenth-century university "the ultimate symbol of male dominance." In her study of southern state-supported universities, McCandless argues that South Carolina vehemently resisted coeducation in the 1890s. The experience of Furman University, which was then a Baptist-affiliated institution in Greenville, South Carolina, suggests that the state's relationship with coeducation was more nuanced and complex. Furman's faculty adopted the policy voluntarily in 1893, and students celebrated Furman's status as the first white coeducational college in the state. Students welcomed women into academic and social life, but often in ways that reaffirmed those women's "proper," passive roles as southern ladies. The women themselves, however, found ways to subvert gendered expectations and to claim a place for themselves on campus and in their communities. Though Furman's experiment with coeducation ended after only seven years, it complicates the standard historical narrative in important ways. It suggests that support for coeducation in South Carolina was stronger and more widespread than previously recognized. It reveals the competing meanings ascribed to coeducation, both among its supporters and its opponents, and it reveals the policy's conflicting consequences--reinforcing traditional gender conventions while providing women (and men) with the language to redefine them.

Key Words: coeducation, gender, Furman, South Carolina

My paper argues that the myth of the Thomas Jefferson-like rural plantation owner, accompanied by a mistress who governed the interior spaces of the “big house,” does not fully reflect the different kinds of slaveries and masteries that emerged in light of a growing market and urban economy in early Republican Virginia. While historians have studied manufacturing and slave renting in rapidly industrializing cities like Richmond and Alexandria during these decades, few have examined women’s roles in these enterprises. I contend that women like Catharine Flood McCall—a spinster who rented her slaves for a profit and owned slave-manned two nail manufactories—could serve as masters over their urban slaves, even while living far away from the sites of slave labor, because of their social dependence on white male liaisons. I ultimately argue that women like McCall—who was the largest female slave owner in a county where over 90% of women owned slaves—helped to entrench the system of slave labor despite the growth of wage-based labor in early Republican urban Virginia.

Key Words: Slavery, Early Republic, Women/Gender, Urban South

In the field of Victorian literary studies, George Eliot’s supernatural tale “The Lifted Veil” (1859) remains one of the most overlooked works of her canon, which is surprising considering its notable resemblance to Stephenie Meyer’s popular novel "Twilight" (2005). Both works feature teenage boys with supernatural powers taking an interest in girls whose minds they cannot read. Despite the close similarity of their works, Meyer and Eliot diverge in terms of how they portray the hero’s yearning to achieve telepathic union with his lover. Meyer taps into what John Durham Peters defines as the romantic longing to rise above the material body and achieve spiritual union with one’s lover via thought transference. Therefore, she represents Edward’s wish to read Bella’s mind as a touching desire to gain access to the most intimate parts of his beloved’s psyche. In contrast, Eliot illustrates the nightmare version of this romantic notion by showing how her main character, Latimer, commits a disturbing violation against his wife, Bertha, in reading her innermost “soul.” In my presentation, I argue that Eliot interrogates the myth of knowing what is on your lover’s mind through Bertha’s growing fear when she realizes her husband can take complete control of her. Eliot’s supernatural tale constitutes a lens through which we can critique an unhealthy version of romantic love that results in a woman losing her sense of self, personal identity, and independence.

Key Words: romance, marriage, the Gothic, women writers, Victorian Britsh literature

vermorrow : no attack in progress (2015) for percussion duo and video is a sonification of the 257 fatal shootings incidents of civilians by American on-duty police officers in 2015 where The Washington Post reported no attack was in progress or the threat level was undetermined at the time of the shooting. My talk will explore the ethics and aesthetics of my compositional decisions in creating the relational work of sound art and will attempt to analyze those decisions and the work through two feminist critical frameworks.

Key Words: sonification, data, feminism, critical theory

As one of the most controversial yet successful books of 2015, Between the World and Me by Ta-Nehisi Coates reflects upon the psychological, socio-econonomic, and political consequences present in the Black community from the undervalued and underrepresented race-critical perspective. Coates, a MacArthur Genius grant recipient and Atlantic journalist, illumines marginality as a site for political and cultural resistance. Coates’ prophetic jeremiad—read by President Barack Obama and lauded by Toni Morrison as necessary reading—considers the narrative of the so-called liberal American Dream but with a scrutinizing eye for its collateral damage. Yet, critics have included such prominent figures as Princeton Professor and Black activist Cornel West. This paper examines the nature of the controversy and claims surrounding Coates’ widely reviewed book and attempts to understand dynamic responses to Coates within and against the legacy of Martin Luther King Jr. Does Coates present King in unfairly harsh terms? How have Black critics responded to Coates as underappreciating the political organization and social utterance of King? What can be gained by renewed reflection upon the ever-evolving conversation in the Black community on the body and the means of political involvement? This paper will reflect upon these themes with close textual and historical analysis.

Key Words: lack Theology; Ta-Nehisi Coates; Martin Luther King Jr

Huntington’s Disease (HD) is a neurodegenerative disorder that is caused by an expansion of CAG repeats that encode a polyglutamine (polyQ) stretch in the Huntingtin (Htt) protein. Although this mutation was discovered 20 years ago, there is still no effective treatment or cure for HD. Htt is a large scaffolding protein (~350 kD) that is involved in multiple cellular functions. The polyQ stretch sits adjacent to a 17 amino acid N-terminal domain (N17) that forms an amphipathic helix capable of influencing polyQ structure and function. The N17 domain is highly conserved in vertebrates, and enables Htt to interact with membranes and organelles. It is also the target for a number of post-translational modifications that can influence Htt function and the pathogenesis of mutant Htt. Additionally, in vitro experiments demonstrated that the N-terminal domain may regulate Htt’s function in autophagy. To explore further the contribution of the N17 domain to critical Htt functions in vivo, I generated a knock-in mouse model expressing a version of Htt lacking the N17 domain (Htt?N17). Mice homozygous for the N17 deletion (Htt?N17/?N17) are born at normal Mendelian frequency, and behavioral testing indicates that the deletion of the N17 domain results in learning and memory deficits. I am currently examining the potential role of the Htt N17 domain in regulating Htt’s function in autophagy in vivo. Furthermore, I am assessing the potential for the ?N17 deletion to modulate HD mouse model pathogenesis in trans, by characterizing Htt140Q/?N17 mice. These analyses should provide much needed information about the contribution of the N17 domain to normal Htt function, and its role in modulating HD pathogenesis.

Key Words: Neurodegeneration, behavioral characterization, autophagy modulation

Stability of atherosclerotic plaques, which occlude arteries, is of great clinical importance as plaque rupture can result in heart attack or stroke; leading causes of death in the US. In response to atherosclerosis, it is widely believed that smooth muscle cells (SMC), which comprise the artery wall, increase their migratory and proliferative capacity and invade the neointima where they secrete plaque stabilizing extracellular matrix (ECM). We previously identified that collagen, type XV, alpha 1 (COL15A1) expression is increased in human atherosclerotic plaques and is associated with plaque burden. COL15A1 has been shown to link large fibrillar collagens to confer ECM stability. Of interest, siRNA knockdown of Col15a1 in cultured human SMC results in a decrease in proliferation and an increase in migration of SMC. Taken together, we hypothesized that SMC-derived COL15A1 is critical in atherosclerosis through promoting plaque stabilizing ECM organization. To test this, we generated and placed inducible SMC specific Col15a1 knockout (SMC-Col15a1KO) and wild-type (SMC-Col15a1WT) mice on an atherogenic diet for 18 weeks. We discovered that SMC-Col15a1KO exhibited a drastic decrease in overall plaque (~4 fold) and artery (~1.5 fold) size. SMC-Col15a1KO have a decrease in overall plaque collagen content (~3 fold) and collagen fiber maturation. Moreover, SMC-Col15a1KO demonstrated a decrease in overall plaque cell number (DAPI+, ~2 fold) and a decrease in plaque SMC proliferative capacity in vivo (~2 fold). Together, these studies provide the first evidence that a SMC derived collagen, COL15A1, is a significant and novel player in advanced atherosclerotic plaque progression and stability.

Key Words: collagen, atherosclerosis, smooth muscle cells

Insulin access to the brain may be critical for appetite regulation, metabolism, and cognition. Prior work suggests insulin crosses the blood-brain barrier (BBB) to reach brain interstitial fluid where it can act on neurons. Little is known about insulin transit in the BEC and if insulin resistance affects it. We tested whether BECs have an insulin receptor (IR)-mediated vesicular transport system and if high-fat diet (HFD)-induced insulin resistance affects this. We fed rats HFD or normal chow (ND) for 4 weeks before isolating and culturing BECs. We examined BEC insulin uptake using radiolabeled insulin (125I-ins), insulin signaling, and mRNA and protein expression. 125I-ins uptake was decreased in BECs from HFD rats compared to ND (p<0.01) despite similar signaling in both groups after insulin treatment. IR-β mRNA and protein were not significantly different between HFD and ND. We then used cell-surface biotinylation and western blotting to test whether insulin affected IR-β endocytosis. Plasma membrane sheets were isolated from rat microvascular BECs treated with 10 nM insulin or vehicle. Compared to vehicle, insulin treatment decreased plasma membrane-bound IR-β indicating receptor-mediated endocytosis. Blocking PI3-kinase or MEK pathways decreased insulin signaling in whole-cell lysates, but did not prevent IR-β endocytosis. This is consistent with our previous findings that blocking these pathways did not decrease 125I-ins uptake. In conclusion, insulin promotes BEC insulin uptake by stimulating IR-β endocytosis. HFD feeding reduced 125I-ins uptake despite preserved insulin signaling. These findings underscore the need to unravel the precise mechanisms regulating insulin uptake in BECs.

Key Words: insulin resistance, metabolism, blood-brain barrier

Alzheimer’s disease (AD) is a devastating neurological disorder characterized by progressive memory loss and cognitive decline. In the United States alone, it is the sixth leading cause of death, and is the only disease among those in the top ten still with no cure or disease-modifying treatments. At the cellular level of the disease, two proteins known as amyloid beta (A) and tau are both necessary for progression of the disease and neuron death. Although both of these proteins are involved in the pathology of AD, it is still unclear how A and tau interact at the cellular level to cause neuron dysfunction and eventual death. One hypothesis of AD to explain how these proteins are connected at the cellular level is an excess of calcium influx into neurons, or excitotoxicity. One of the ways excitotoxicity is thought to occur is when A binds receptors at the cell surface, such as the N-Methyl-D-Aspartate (NMDA) receptor, allowing excess calcium influx into the neuron. This excess calcium influx disrupts normal calcium signaling events putting stress on the neuron, and eventually leading to neuron death. An early marker of the neuron death in AD is ectopic re-entry of post-mitotic neurons into the cell cycle. Using ectopic cell cycle re-entry as a read-out for amyloid toxicity, my project seeks to elucidate the role of calcium and cell cycle re-entry in the neuronal of Alzheimer’s disease.

Key Words: Alzheimer's, Neuroscience, Cell Signaling

Adenosine is an important neurochemical responsible for protecting tissue during hypoxic events, such as stroke, and for modulating the activity of other neurotransmitters. Previous work has primarily looked at variations in adenosine concentration over the course of several minutes to hours. Fast-scan cyclic voltammetry (FSCV) can be used to measure neural adenosine activity with sub-second temporal resolution. Recently, spontaneous, transient adenosine events have been characterized by the Venton lab in anesthetized rats and have been found to be regulated in part by the inhibitory adenosine A1 receptor. However, there are several other possible receptors and channels that could affect the release and clearance of transient adenosine events. Unfortunately, many pharmacological agents that could be used to probe these pathways are either not readily available or don’t cross the blood-brain barrier. Experimenting in brain slices allows us to supplement in vivo work and combat the latter issue. In this work, adenosine transients were characterized in brain slices of the pre-frontal cortex (PFC) and thalamus. Transient adenosine in the PFC had concentrations of 0.13 (+/- 0.01) µM and lasted for 3.4 (+/- 0.1) seconds which agrees with transients observed in vivo. In the thalamus, transients have an average concentration of 0.11 (+/- 0.01) µM and last 7.5 (+/- 0.4) seconds. Knowing the characteristics of transient adenosine events in brain slices allow for a more complete analysis of the biological pathways that control them.

Key Words: adenosine, electrochemistry, neuroscience, voltammetry

Retinitis pigmentosa is cluster of related disorders that cause progressive vision loss due to photoreceptor degeneration. One cause of retinitis pigmentosa is dysfunction of the retinal-pigmented epithelial cells (RPE). RPE play many roles in maintaining photoreceptor function, including the daily phagocytic removal of aged photoreceptor outer segments (POS). The phosphatidylserine (PtdSer) receptor MerTK is expressed by RPE and is critical for this process. Loss of MerTK impairs POS clearance and causes subsequent photoreceptor degeneration. The goal of our research is to understand the pathophysiology of retinitis pigmentosa linked to MerTK mutations. Specifically, whether MerTK is important for mediating the physical engulfment of photoreceptor outer segments or if it plays a more complex signaling role. To address this question, we generated mice that lack MerTK but over express the PtdSer receptor BAI1 (MerTK-/-BAI1Tg). BAI1 is a functional analog of MerTK in regards to its ability to mediate PtdSer dependent engulfment but it initiates a different downstream signaling pathway. We have been monitoring the retinal degeneration in MerTK-/-BAI1Tg mice by analyzing retinal histology. In addition, we have developed models to assess the engulfment capacity of RPE. Our preliminary analysis of two-month old MerTK-/-BAI1Tg mice found that they exhibited comparable retinal degeneration relative to MerTK-/- mice. These data suggest that BAI1 is incapable of rescuing retinal degeneration linked to MerTK mutations. Should we find that RPE from MerTK-/-BAI1Tg are capable of engulfing more POS than MerTK-/- RPE, it will suggest that MerTK’s role in the RPE extends beyond the physical mediation of POS engulfment.

Key Words: phagocytosis, retina, retinitis pigmentosa, retinal pigmented epithelium

Adenosine is an endogenous nucleoside that modulates important physiological processes, such as vasodilation, in the central nervous system. A rapid mode of adenosine signaling on the second time scale has been recently discovered, but the ability of this type of adenosine signaling to rapidly modulate blood flow has not been characterized. In this study, the effect of transient adenosine release to cause vasodilation was evaluated by simultaneously measuring adenosine and oxygen using fast-scan cyclic voltammetry. Oxygen changes occur when there is an increase in local cerebral blood flow and thus are a measure of vasodilation. About 34% of adenosine transients in the rat caudate-putamen caused a subsequent transient change in oxygen. The amount of oxygen was correlated with the concentration of adenosine release and larger adenosine transients (over 0.4 uM) always caused oxygen changes. The average duration of adenosine and oxygen transients were 3.2 seconds and 3.5 seconds, respectively. On average, spontaneous adenosine peaks 0.2 seconds prior to the peak in oxygen. The A1 antagonist, 8-Cyclopentyl-1, 3-dipropylxanthine (DPCPX), significantly decreased the concentration of spontaneous adenosine release and consequently oxygen release also decreased. The A2a antagonist, 2-(2-Furanyl)-7-[3-(4-methoxyphenyl) propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH442416), decreased the number and frequency of both adenosine and oxygen release. These results demonstrated that adenosine-induced vasodilation was modulated via A2a receptors. Adenosine can modulate blood flow on a rapid, sub-second time scale, a novel finding that rapid adenosine changes can induce rapid, but transient, vasodilation.

Key Words: denosine; Oxygen; in vivo; blood flow; Fast scan cyclic voltammetry

The pathogenic bacteria Neisseria gonorrhoeae and N. meningitidis induce their own phagocytosis into human host cells prior to replication. Bacterial cell entry is promoted by the binding of Neisserial outer membrane opacity-associated (Opa) proteins to human carcinoembryonic antigen-like cell adhesion molecule (CEACAM) receptors, a widely-distributed class of cell receptors in the human body. Binding of Opa proteins to either CEACAM1, CEACAM3, CEACAM5, or CEACAM6 generates intracellular signalling events which lead to bacterial internalization by both phagocytes and epithelial cells. We are interested in determining whether purified and folded Opa proteins stabilized in liposomes retain the ability to promote liposomal entry into epithelial cells similar to Neisseria. The ability to target CEACAM+ cells for Opa proteoliposome uptake may prove valuable in targeted therapeutic delivery. Our results demonstrate that Opa-proteoliposomes target surface CEACAM receptors on transfected HeLa cells for binding and preliminary data indicate the liposomes are taken into the cells. This internalization is dependent on metabolic energy, suggesting the cells may employ active-uptake mechanisms to internalize the liposomes. Our work shows that Opa proteoliposomes deserve further consideration as a platform for targeted delivery to CEACAM-expressing cells.

Key Words: Therapeutic delivery, cell targeting, liposomes

Important derivatives synthesized from polycyclic aromatic hydrocarbons (PAHs) (e.g., benzene, naphthalene, and anthracene) include the alicyclic family. These derivatives are often found as antimalarial and antitumor agents as well as topical analgesics. However, due to their innate stability, a characteristic of their aromatic nature, PAHs are difficult to modify. This obstacle can be overcome through the use of a pi-base (i.e., {TpMo(NO)(L)}) which donates electron density from the metal into the arene, disrupting aromaticity, and making the arene prone to derivatization. Through tandem electrophilic, nucleophilic additions and subsequent removal of the metal complex through oxidation, the isolation of novel small compounds is easily achieved. {TpMo(NO)(L)} allows for the use of iodine to enact a clean oxidative decomplexation, providing the free organic (average of 60% yield) and returning the Mo(I) precursor used to prepare the initial η2-aromatic complex (average of 80% yield). Previously this approach was shown to be successful utilizing N-methylimidazole as the ancillary ligand, L; however, to further develop a more diverse synthetic utility, N,N-dimethylaminopyridine has been used to isolate an allyl of naphthalene and anthracene allowing for the addition of nucleophiles in the absence of acid, thus preventing the lack of reaction failure due to nucleophile quenching. Recent discoveries have shown the ability to bind two new cores, pyridine and trifluorotoluene, which provide the potential to form novel organics with a thoroughly investigated record of biological activity. In particular, the common trend of increased lipophilicity with fluorine substitution gives the investigation of this new system great precedence.

Key Words: Organometallic, catalysis, small molecule synthesis

The stereostructure of polymeric chains can greatly influence their physical and chemical properties. Therefore, controlling the stereostructures (tacticity) of polymers is very important in materials chemistry. There have been numerous studies on how to control the tacticity of polymer during a radical polymerization process. However, only a few monomers can be applied to stereospecific living radical polymerization. A Lewis acid–mediated stereocontrolled atom transfer radical polymerization (ATRP) of various acrylamide monomers was successfully achieved by using the newly designed catalysts. Schiff base-based macrocylclic compounds were synthesized from the condensation of an aryl dialdehyde with achiral and chiral diamines. These macrocyclic Schiff bases and their corresponding reduced macrocyclic amines were used as the ligands for the ATRP. The polymerization was conducted in methanol by using the copper(I)-macrocyclic ligand complex as the catalyst and ethyl 2-bromoisobutyrate as the initiator in the presence of 5 mol % Yb(OTf)3 at room temperature (20?). Polymers with high isotacticty and narrow polyisodispersity index (PDI) were obtained along with high conversion of the monomers. The resulting poly (N,N-dimethylacrylamide) had an isotacticity as high as 90% and a PDI of 1.05. The resulting poly (N-isopropylacrylamide) had an isotacticity as high as 89% and a PDI of 1.12. It is the first time that the copper-mediated stereocontrolled ATRP of N-isopropylacrylamide was successfully achieved.

Key Words: Polymerization, macrocyclic ligands, acrylamides

Currently a worldwide effort is going on to make Quantum Computers, if made they would be able to solve some types of problems infinitely faster than our present computers and revolutionize computing. The biggest hurdle in making these Computers is that they are extremely sensitive to external noise given they work at the atomic scale. In my research we exploit some strange properties of Quantum Mechanics and the mathematical field of topology to make quantum knots; these knots are insensitive to deformations and external noise. Electrons have a strange property of storing their geometric path when traversed around a magnetic field, we can engineer ‘quasiparticles’ by attaching small fluxes on particles and braid them around each other. As the particles store their geometric paths, we can make unique knots by braiding these ‘quasiparticles’ around each other. Recently materials have been discovered which can sustain exotic 'quasiparticles' that can be used to braid knots experimentally. These quantum knots can correspond to different computing operations and as these knots are robust we can make Quantum computers insensitive to external noise.

Key Words: Quantum Computing, Topological phases, theoretical physics

The scorpionate class of ligands has been used for a variety of applications from catalysis to the bioinorganic modeling of enzymatic active sites. The original scorpionate, tris(pyrazolyl)borate (Tp), has since seen many derivatives due to the desirable characteristics it imparts onto the resulting metal complexes, which is illustrated with thousands of publications featuring the scorpionate ligand class. The focus of this work is the elaboration upon the previously reported Tz analog (tris(triazolyl)borate), including optimization of its synthesis and expansion of its moderate synthetic scope. The Tz ligand offers an important advantage over its Tp predecessor, as it can undergo modulation of its properties through changes to the environment of the resulting metal complexes. The electronics of metal complexes incorporating this ligand can conceivably be tuned by changes in solvent (through hydrogen bonding), as well as changes to pH (through protonation of the lone pair of electrons on each ring, up to three possible protonations). These characteristics would be ideal for modelling of biological systems, which are often controlled by similar mechanisms, as well as for modulation of catalysts and other synthetic reagents. This is currently under investigation by the direct comparison of Tz and Tp systems with the group 6 metals molybdenum and tungsten. The resulting metal complexes are being investigated with a variety of electronic environments and oxidation states to find the ideal characteristics for the modulation of their properties. Advances in the tuning of these complexes opens the doors for their uses from enzymatic models to chemical switches.

Key Words: scorpionate, bioinorganic, catalysis, chemical sensor

The increasing global demand for fossil resources has sparked a renewed interest in new catalytic technologies for the conversion of hydrocarbons from petroleum and natural gas to higher value chemicals. For example, styrene is produced from benzene and ethylene on a scale of approximately 18.5 million tons annually. The current route for styrene production involves acid-catalyzed formation of ethylbenzene, trans-alkylation to optimize the yield of mono-functionalized product, and dehydrogenation of ethylbenzene. The direct oxidative conversion of benzene and ethylene to produce styrene could provide a more efficient route, but catalysts that have been developed previously for this transformation suffer from low selectivity and/or low yields. The new rhodium catalyst (^FlDAB)Rh(TFA)(𝜂²–C₂H₄) [^FlDAB = N,N’-bis(pentafluorophenyl)-2,3-dimethyl-1,4-diaza-1,3-butadiene; TFA = trifluoroacetate] converts benzene, ethylene and air-recyclable Cu(II) oxidants to styrene with yields ≥ 95% (based on Cu(II) as the limiting reagent) and with quantitative selectivity. Turnover numbers > 800 have been demonstrated with catalyst stability up to 96 hours. A combined experimental and computational study has been employed to elucidate mechanistic features of this unique catalytic process.

Key Words: Catalysis, rhodium, styrene, hydroarylation, energy

Linear alkylbenzenes (LAB), such as 2-phenyldodecane, are widely used industrial chemicals (production of over 2700 kilotons/year) which are commonly found in detergents and plastics. Due to environmental degradation concerns the development of LABs has evolved with a focus on generating straight alkyl chains. However; because of the industrial methodologies using strong acid based mechanisms generating truly LABs is not possible; due to the carbocation intermediate. Moreover, in petrochemicals a LAB can be branched in the 2 position but is still called a LAB due to the carbocation issue. This limitation has led the Gunnoe laboratory to study organometallic based catalysts that operate via a metal mediated mechanism, thus avoiding the carbocation intermediate, which can produce super linear alkylbenzenes (sLAB). Recently we published a paper detailing a new rhodium complex that can directly and selectively produce styrene from benzene and ethylene. Studying this catalyst with longer chained olefins has led to the development of new rhodium catalysts. Through structure and activity relationships we have designed a novel catalyst that achieves the best linear to branched selectivity yet discovered. The unmatched selectivity of these catalysts directly from unfunctionalized substrates could lead to a huge number of new possibilities from plastics to fragrances to detergents.

Key Words: CH activation, industrial, linear alkylbenzenes

I will present a new survey of 33 GHz radio continuum emission from local U/LIRGs carried out using the Karl G. Jansky Very Large Array (VLA). This is the first such survey and it combines high resolution, good sensitivity, and multi-configuration observations that should have sensitivity to emission on all spatial scales. (Ultra) luminous infrared galaxies host some of the most extreme star-forming environments in the local universe, with large reservoirs of molecular gas and dust concentrated in the central few kpc. Our VLA observations allow us to see through the dust in these systems to resolve the sizes of their active regions, which is essential to understand the surface and volume densities of star formation and gas in these extreme systems. I will present the best size measurements to date of the active regions for our 22 targets. I will show what these sizes imply about gas volume and surface density and infrared luminosity surface densities. I will also lay out the physical implications of these values for the strength of star formation and feedback (especially radiative feedback) in extreme environments.

Key Words: Star Formation, Extragalactic, Radio interferometry

Gltph is a sodium dependent aspartate transporter from archaea that is structurally homologous to glutamate transporters and, therefore, provides a model for excitatory amino acid transporters (EAATs). Crystal structures suggest a model for transport, but do not provide structures for intermediate or transition states that must mediate transport. Moreover, conditions that are used for crystallography may drive the protein into conformations that are not highly populated in bilayers under conditions that support transport. In the present work, distance distributions were measured for Gltph in bilayers though site directed spin labelling (SDSL) and double electron-electron resonance (DEER) to determine if the crystal structures are representative of biologically relevant conformations. Distances were measured both across the subunits of the trimer and within an individual monomer. The protective osmolyte sucrose was used to modulate the populations of individual states and to determine if the conformational states observed by pulse EPR in bilayers were in equilibrium. Distance distributions for the single mutant S278R1 on hairpin loop (HP) 1 revealed three populations with average distances that were close to distances predicted from crystal structures. However, the width of the distance distributions suggests that there are biologically relevant states that are not seen in the crystal structures. The distributions were altered in the presence of sucrose, favoring shorter distances and narrower distributions. These sucrose mediated effects were not equivalent between substrate loaded states or the empty transporter, suggesting that either the conformational equilibrium or the rates of interconversion between states may be modulated by substrate binding.

Key Words: substrate transport, conformational exchange, EPR

Intracranial aneurysms (IAs) are a prevalent and serious condition. Ruptured aneurysms account for 3-5% of new stroke cases each year. The most common treatment to prevent rupture is endovascular coiling, yet 30% of IAs recur after treatment. Recurrence correlates with poor clot remodeling and fibrin coverage. These outcomes are influenced by factors including properties of the coil wire, coil packing density and hemodynamics. In vivo studies have examined thrombosis at long-term endpoints, but the sensitivity of clot structure to flow profile and coil arrangement is not well understood. Our current research aims to use in vitro models to better understand how coil wire shape and placement affect clotting under flow in order to develop coil designs that improve healing. Platelet-rich plasma (PRP) clots were formed on coiled wire and braided wire coils under arterial hemodynamics similar to that at a bifurcation aneurysm neck. Scanning electron microscopy and confocal imaging show higher fiber polymerization on braided wire than coiled wire, but higher platelet coverage on coiled wire. A novel bifurcation aneurysm flow chamber was constructed to elucidate the relationship between coiling and clot formation in an aneurysm under flow. At constant packing density, coiled wires arranged parallel increased fibrin polymerization rate in the aneurysm dome compared to a circumferential arrangement or braided wire in either arrangement. These results indicate that flow patterns shaped by coil placement and coil wire shape impact clot formation throughout the aneurysm, which could modulate subsequent IA healing and recurrence.

Key Words: Hemodynamics, cerebral aneurysm, endovascular device

We present a Hubble Space Telescope (HST) analysis of the age and mass distribution of bright, optically-visible star clusters in a sample of 27 local luminous infrared galaxies (LIRGs). These galaxies host the most extreme star-formation in the local Universe, with their observed activity primarily triggered by the interaction or merger of gas-rich disk galaxies. We constructed extinction-corrected color-color diagrams of all star clusters found in each galaxy and compared the observed colors with predictions from the Bruzal & Charlot (2003) Simple Stellar Population Models. We find that, for an instantaneous starburst and Salpeter IMF, the derived cluster ages imply a disrutpion rate in these galaxies that appears to be consistent with what is seen in the Antennae, indicating the general influence mergers have on the creation and destruction of star clusters. The cluster disruption rate measured also stands in constrast to what is found for lower mass, less star forming systems in the local Universe, implying that different galactic environments produce funademtally different cluster disruption laws. For LIRGs with detailed dynamical modeling, we also find that their oldest clusters have ages consistent with the time since pericentric passage. Finally, the derived cluster masses imply an initial mass function for the sample that is broadly consistent with SFR-normalized mass functions for a wide range of star-forming galaxies in the local Universe. This study is part of the Great Observatories All-Sky LIRG Survey (GOALS).

Key Words: Galaxy Mergers, Star Clusters, GOALS

Outer-membrane TonB-dependent transporters function in the uptake of essential nutrients, and are important for the success of many pathogenic bacteria. During transport, these proteins undergo a cycle of binding and unbinding to the inner membrane protein TonB, through an interaction that is mediated by the Ton box, an energy-coupling segment near the transporter N-terminus. Over 50 high-resolution crystal structures have been obtained for 12 different TonB-dependent transporters, however the mechanisms of substrate transport remain unclear. Determination of membrane protein structure or dynamics with high resolution using highly heterogeneous native systems is an attractive way to solve transport mechanisms. In this work, the cobalamin transporter BtuB was overexpressed and spin labelled in outer membranes, interspin distances were measured to a spin labelled cobalamin and between outer loop positions using pulse EPR. A comparative analysis of the data reveals a similar interspin distance distribution between outer membranes and synthetic vesicles. We then take advantage of these native lipid environments to study the effects of TonB binding. There is evidence of TonB mediated allosteric loop modulation; the binding of TonB to the Ton box on the periplasmic surface of BtuB alters the configuration of these extracellular loops. CW EPR measurements using a spin labeled substrate show TonB binding lowers the affinity of the transporter for the substrate. Taken together these data indicate a clear TonB effect transduced from the periplasmic Ton Box to the substrate binding pocket and loops on the outer surface of the transporter.

Key Words: EPR, native systems, protein dynamics

The bacterial host factor Hfq is an RNA-binding protein that facilitates the interaction of mRNAs with small regulatory RNAs (sRNAs) and acts as a central hub of transcriptional regulation. Hfq has been linked to numerous pathways including stress response, quorum sensing, and biofilm formation. Bioinformatic evidence suggests that several species of bacteria may possess a second Hfq paralog, though the function of this second copy is unknown. Two potential Hfq homologs (denoted here as Hfq1 and Hfq2) have been identified in the genome of the deep-branching thermophile Aquifex aeolicus (Aae). To compare the structure and function of Hfq1 and Hfq2, as well as elucidate any potential interactions between them, the proteins have been over-expressed, purified, crystallized, and biochemically characterized. The structures of Aae Hfq1 and Hfq2 have been determined to 1.5 and 2.0 Å resolution (respectively). Aae Hfq1 has also been co-crystallized with two nucleotides of uridine in a newly defined lateral binding pocket. While the overall structures of both proteins are similar, the RNA-binding profiles of the two homologs are found to be quite different; Aae Hfq2 displays increased binding at low pH and is found to bind RNA as well as DNA in vivo.

Key Words: Protein Crystallography, RNA-binding, Aquifex

Stars are not always stable. Recently, a handful of extremely low-mass white dwarfs (ELM WD, only about 20% of the solar mass) have been discovered to exhibit g-mode pulsations, which is driven by buoyancy. One particular ELM WD, J1112, has been observed to pulsate at periods so short that the pulsations may be another kind of mode (p-mode, the restoring force is pressure), making this star unique among all WD pulsators. Since the ELM WDs are thought to be formed only through binary, and not single star evolution, the observed periods give the opportunity to constrain the interior structures of them. I will discuss our recent efforts to construct models of these ELM WD pulsators using the MESA stellar evolution code to carry out binary evolution. The relative size of the solar-composition envelope to helium core is expected to vary significantly with stellar mass and orbital period. This variation in structure is reflected in the oscillation mode periods for the models. Lastly, I will discuss constraints on the interior structure of J1112 from seismology.

Key Words: white dwarfs, seismology, binary evolution

While both exoplanets and stellar-mass companions have been found in extremely short-period orbits, there has been a paucity of brown dwarf (BD) companions orbiting Sun-like stars, a phenomenon known as the "Brown Dwarf Desert." However, more recent work has shown that this Desert might be limited in extent, only existing for small separation (a < 5-10 AU) companions, and may not be as "dry" as initially thought. It has been previously suggested that there may be an "F Dwarf Oasis," where the BD Desert observed for Solar-like stars ceases to exist for F dwarf stars. The Sloan Digital Sky Survey (SDSS-III) Apache Point Galactic Evolution Experiment (APOGEE) has compiled a catalog of ~400 of its most compelling stellar and substellar companion candidates orbiting host stars of various spectral types and evolutionary states. Among these candidates, approximately 100 had a derived companion mass in the BD regime (13-80 MJup), which is a significant increase compared to the number of known small separation (a < 1 AU) BD companions. Our sample appears to manifest the BD desert, but only for seperations < 0.2 AU rather than the previously held 5 AU. This is explained by one of the unique qualities of our sample when compared to previous companions surveys: Two-thirds of the BD candidates in our sample are orbiting evolved stars, most of which were F dwarfs during their main sequence lifetime, consistent with the notion of an F Dwarf Oasis. Using this sample, we further test this hypothesis by constraining the formation mechanisms of BD companions, and exploring their orbital evolution as their host evolves off the main sequence.

Key Words: exoplanets, brown dwarfs, evolved stars

Diacylglycerol Kinase α (DGKα) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Recent work has demonstrated that DGKα activity is at a central tumorigenic node and the attenuation of its activity by a small molecule inhibitor, R59022, has shown promising results in countering glioblastoma multiforme (GBM) growth both in vitro and in vivo (Dominguez, et al, 2013). Until recently, R59022 and R59949 have been the only described inhibitors of DGKα. We have identified a serotonin receptor antagonist, Ritanserin, which is almost structurally identical to R59022. Our data show that Ritanserin is a more potent inhibitor of DGKα activity than R59022 in vitro. We have additionally investigated the specificity of Ritanserin for DGKα over other mammalian DGKs, and the affinity of R59022 for serotonin receptors. Since Ritanserin has previously been used clinically, and shown to have a low incidence of adverse side-effects, we believe that it could be a viable therapeutic agent for treatment of GBM. Additionally, our work sets the stage for the development for more potent DGKα inhibitors.

Key Words: Ritanserin, Diacylglycerol Kinase, Glioblastoma Multiforme, R59022

Previous studies have identified a novel food allergy driven by IgE antibodies specific for galactose-α-1,3-galactose (alpha-gal), and oligosaccharide found in red meat. While it is known that B cells play an important role in allergy as the producers of IgE antibodies that drive the allergic response, these B cells have yet to be described. The number of markers required to identify the major B cell subsets precludes a more detailed analysis of these cells by flow cytometry and may prevent the discovery of unique phenotypes present in allergic individuals. We have addressed this problem by using of mass cytometry (CyTOF), which enables the simultaneous analysis of up to 40 markers in a single staining panel. Here we analyzed the expression of 23 cell surface markers in PBMCs from 19 alpha-gal-allergic patients and 20 non-allergic controls by CyTOF. Additionally, we combined our CyTOF data with clinical readouts of allergic status to identify makers that may correlate with allergic disease. Our data reveals substantial heterogeneity within major B cells subsets. Our analysis also identifies a number of markers that vary significantly in their expression in allergic versus non-allergic B cells. These findings show the power of expanding the panel of markers used to identify cellular subsets and identify unique B cell populations that differ between alpha-gal allergic and non-allergic individuals.

Key Words: Immunology, Allergy, B cells

Natural killer (NK) cells are regulated by an array of activating and inhibitory receptors that interact with ubiquitously expressed MHC I molecules. Specific NK inhibitory receptor interactions with MHC I are associated with improved clinical outcome in response to cytomegalovirus (CMV), adenovirus and HIV infections. However, the precise role of NK inhibitory receptors in viral immunity is not well understood. We’ve developed a novel mouse model that allows us to interrogate NK-dependent control of murine (M)CMV. This resistance is conferred by the MHC I molecule, Dk, and NK cells bearing its cognate inhibitory receptor (IR). Recently, we have identified an activating receptor (AR) that contributes to MCMV resistance in a Dk-dependent manner. Remarkably, we found that specific blockade of this AR abrogates Dk-dependent NK-mediated resistance to MCMV. Moreover, a significant fraction of AR+ cells coexpress IR, and coexpressing NK cells show dramatically enhanced proliferation compared to NK cells only expressing AR in response to MCMV. These data suggest that cooperation between activating and inhibitory MHC I receptors have a profound influence on NK cell detection and clearance of virus-infected cells. This work will provide insights into NK cell biology that may be exploited in the future for immunotherapies.

Key Words: Immunology, Virology,

Both professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and other particles on a daily basis in vivo. Since professional and non-professional phagocytes reside in proximity in essentially all tissues, a fascinating unanswered question is whether there is cross- communication between phagocytes in mediating cell clearance, and how this might impact inflammation and tissue function. Here, we show that macrophages, via the release of a soluble growth factor and microparticles, can influence the nature of engulfment by non- professional phagocytes and their response. During apoptotic cell engulfment or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor-1 (IGF-1). The binding of IGF-1 to IGF-1r on non-professional phagocytes, redirected their phagocytosis such that the engulfment of larger apoptotic cells was dampened while the uptake of microparticles was enhanced. In contrast, macrophages were refractory to this IGF-1 mediated engulfment modulation. Macrophages also released microparticles, whose uptake (enhanced via IGF-1 signaling) by epithelial cells dampened their inflammatory cytokine production. Consistent with these observations, deletion of the IGF-1 receptor specifically in airway epithelial cells in vivo resulted in exacerbated lung inflammation in response to an airway allergen. These genetic and functional studies reveal a novel IGF-1 and microparticle-dependent communication between macrophages and epithelial cells that can critically influence the magnitude of tissue inflammation in vivo.

Key Words: Phagocytosis, macrophages, IGF-1, apoptotic cells

In the United States alone, peripheral arterial disease (PAD) results in $21 billion in total costs annually and is the leading cause of lower limb amputation. Globally, it is estimated that over 202 million people have PAD. PAD arises when atherosclerotic plaques block arteries in the lower limbs, thereby limiting blood flow to the distal tissue. A promising, but unfulfilled, therapeutic approach to restore distal blood flow is to stimulate the growth of the patient’s own pre-existing collateral arteries that bypass the occlusion(s) (i.e. arteriogenesis). Our lab has recently discovered a subset of collateral artery segments in the mouse that undergo a disproportionate amplification of arteriogenesis in the presence of an occlusion. Moreover, we have identified microRNA-199a-5p as significantly down-regulated in endothelial cells exposed to these “amplified arteriogenesis” flow conditions in-vitro. We therefore hypothesized that the inhibition of microRNA-199a-5p would enhance arteriogenesis following arterial occlusion. To test this, Balb/c mice were treated with either anti-microRNA-199a-5p or non-targeting control oligonucleotide immediately following femoral arterial ligation (FAL). We found that anti-microRNA-199a-5p markedly reduced microRNA-199a-5p expression by 60%, 7 days post-FAL (p<0.01, n=4). By day 21 post-FAL, while distal blood perfusion remained impaired in controls, it had completely recovered in anti-miR-199a-5p treated mice (p<0.05, n=6). Moreover, collateral artery diameter was enhanced by 36% in anti-microRNA-199a-5p treated mice compared to controls (p≤0.001, n=6). We therefore conclude that the inhibition of microRNA-199a-5p leads to enhanced perfusion recovery and arteriogenesis following arterial occlusion and could represent a novel approach for the treatment of arterial occlusive diseases.

Key Words: microRNA, arteriogenesis, cardiovascular, endothelial

Conventional T (Tcon) cells are crucial in shaping the immune response, whether it is protection against a pathogen, attack of tumor cells, or prevention of autoimmunity. In each of these settings, regulatory T (Treg) cells can suppress the activation, proliferation, or function of Tcons. It has become clear that in many autoimmune diseases, Tregs are functional yet fail to prevent the Tcon response against self. In contrast, tumors are enriched for Tregs, creating a microenvironment that inhibits anti-tumor Tcon responses. Thus, the aim of this study is to understand the molecular mechanism governing Tcon susceptibility to Treg-mediated suppression and identify potential molecular targets for immunotherapy. Specifically, our research focuses on SHP-1, a negative regulator of T cell signaling. Using a mouse model in which SHP-1 is deleted in T cells, we observed that a greater percentage of SHP-1-/- Tcons respond to stimulation and proliferate compared to wild type in both the absence and presence of Tregs. Tcons from wild type mice injected with an SHP-1 inhibitor also acquired resistance to Treg-mediated suppression, suggesting a direct effect of SHP-1 on susceptibility to suppression. To address the mechanism by which SHP-1 deficiency allows Tcons to resist suppression, we examined the PI3K/Akt pathway. SHP-1-/- Tcons have increased Akt activation, consistent with previous studies suggesting that Tcons with hyperactivated Akt resist Treg suppression. We plan to investigate whether SHP-1 regulates resistance of Tcons to suppression in vivo and target SHP-1 and/or Akt for immunotherapeutic modulation for autoimmune diseases and cancer.

Key Words: Autoimmunity, immunotherapy, T cells

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, yet current treatments are often ineffective. HCC, however, has been shown to be immunogenic. Patients with tumors containing infiltrating, effector T cells have a reduced risk of tumor recurrence following liver transplantation, suggesting that immunotherapy is a favorable treatment option. One way that the immune system surveys cellular health is through the MHC class I processing pathway. Briefly, cytoplasmic proteins are degraded by the proteasome into peptides which are loaded onto MHC class I molecules. MHC:peptide complexes migrate to the cell surface for display where circulating cytotoxic T cells (CTLs) trigger killing of cells presenting antigenic peptides. In cancer, cell signaling becomes dysregulated resulting in aberrantly phosphorylated peptides that can also be recognized by CTLs as antigenic. Therefore, our goal is to identify tumor-specific phosphopeptides expressed in HCC that are capable of eliciting an immune response. To this end, we incorporated STop And Go Extraction (STAGE) tip technology for sample cleanup, effectively shortening the desalting procedure from days to hours, increasing sample recovery, and allowing for sample multiplexing. Additionally, we utilized complementary immobilized metal affinity chromatography enrichment techniques, resulting in drastically increased phosphopeptide identifications. We applied this methodology to over 20 HCC tumor and normal tissue samples and identified hundreds of phosphopeptides, many of which are derived from dysregulated cell signaling pathways. Furthermore, biological testing indicates that these phosphopeptides are capable of eliciting immune responses from CTLs, suggesting that they are ideal candidates for the development of novel cancer immunotherapeutics.

Key Words: phosphorylation, enrichment, cancer, immunotherapy, mass spectrometry

Pancreatic cancer is the 3rd leading cause of cancer-related deaths in the US, with 72% of patients dying within 1 year of diagnosis and a 5-year survival rate of approximately 7%. We have recently discovered that fragmentation of mitochondria, the principle energy source for the cell, promotes pancreatic tumor growth. In order to further investigate the role of fragmented mitochondria in pancreatic cancer, we are utilizing a patient derived xenograft (PDX) mouse model and a genetically engineered mouse model (GEMM). For our PDX model, we have evaluated the levels of the mitochondrial fission protein, Drp1, as well as the mitochondrial appearance in tumors that have been treated with drugs currently undergoing clinical trials. We find that both the expression levels of Drp1 and the mitochondrial morphology change in response to treatment. In our GEMM, we have manipulated two genes- KRAS and P53- that are characteristically mutated in pancreatic cancer, as well as the Drp1 gene, to interrogate the role of mitochondrial fission in tumor progression. Our preliminary data from the GEMMs indicate that loss of Drp1 increases survival for mice with pancreatic cancer. Analysis of cells isolated from those tumors indicates that metabolic differences between tumors with and without Drp1 may underlie the differences in tumor growth we observe. In conclusion, these studies demonstrate that mitochondrial fission promotes pancreatic cancer tumorigenesis and may represent a promising therapeutic target.

Key Words: Mitochondria, Cancer, Mouse Models, Targeted Therapeutics

Both citizenship and the academic study of politicsare animated by complaints about injustice. Citizens use complaints to point out unjust features of their political worlds. Academics study these worlds and complaints. Exclusion, domination, subordination, misrecognition, to name just a few, all provide languages of political complaint. This paper, however, challenges the democratic adequacy of these complaints -- their ability to track genuinely democratic aspirations about the right to have a say in the political life one shares with others -- and develops an alternative language for describing the most salient forms of political injustice: disenfranchisement. While disenfranchisement is most commonly associated with the denial of the right to vote as such, it is nevertheless used in a much wider array of contexts: citizens complain about being disenfranchised even when they are formally guaranteed access to the ballot box, and this paper argues that such complaints track important concerns about the lack of democratic involvement. To elaborate the distinctiveness of this broader sense of disenfranchisement, the paper engages two academic literatures: a literature in political theory charting current debates about the appropriate language of injustice, and a historical literature documenting the vocabularies that historically marginalized populations have used to contest the injustice that they experiences. Arguing that historical complaints about disenfranchisement can enrich contemporary debates, the paper reconstructs Reconstruction-era complaints about disenfranchisement to elaborate its normative force a substantive relevance to contemporary debates about democracy and its failings.

Key Words: democracy, voting, language

The Primary purpose of this study is to understand Russia’s foreign policy and strategy in Central Asia after the collapse of the Soviet Union in the context of “Great Game” among United States, Russia and China. This thesis tries to divide its evolution into several periods, according to Russia's shifting focus, priority and strategy in Central Asia, and summarize the main feature of each period. The historic importance of Central Asia to Russia and Central Asian states’ unique position in Russia’s geopolitical strategy are discussed in the introductory part. This paper then attempts to divide the developing span of Russian foreign policy in Central Asia into three periods:1991-1995, 1995-2001, 2001-present, with the decree on The establishment of the strategic course of the Russian Federation with member states of CIS in 1995 and the “9•11” event in 2001 as two turning points. 25 years after the disintegration of the USSR saw the everincreasing attention Russia paid to Central Asia. The conclusion part of the paper presents the prospect and boundaries of Russia’s expanding influence in Central Asia. In international scale, proximity to the Middle East has brought Central Asia to the top tier of the US’s counterterrorist operation. Regionally, China emerged to be Russia’s major competitor for the large amount of natural resources and market in Central Asia. This paper hopes to offer a summary of Russian foreign policy in Central Asia, which is traditionally an underresearched area. It especially emphasizes to discuss the changes and evolution in the context of international relations.

Key Words: Russian Foreign Policy, Central Asia, Geopolitics

The slogan “Buddha was Born in Nepal” is pervasive in popular and political discourses on Nepali national identity. On the one hand, the claim is frequently deployed as an assertion of a unified and proud Nepal. Nepal’s ownership of Buddha’s birthplace gives it a unique status among the nations of the world and is often linked to descriptions of Nepal as a land of peace and harmony. On the other hand, the claim that Buddha was born in Nepal has been used to disrupt and subvert hegemonic notions of Nepal as a peaceful land of religious harmony and social inclusion. In one type of this subversive usage, the claim questions the dominance of the Hindu majority over members of marginalized religious and ethnic groups. Regional activists have also used the rhetoric of Buddha’s birthplace to draw attention to the oppression of Madheshis and even to challenge the territorial integrity of the Nepali state. All of these dynamics exist in tandem with ongoing discussions of Nepal’s newly-adopted state secularism. By analyzing the ways in which the claim that “Buddha was born in Nepal” is leveraged for divergent political purposes, this article explores the larger debates over secularism in Nepal.

Key Words: Nepal, secularism, cultural anthropology, religion & politics

This research paper examines the creation of Vorkuta as a GULAG labor camp in the Soviet Union as well as the growth of Vorkuta as a town and product of the labor camp. It is located in the most northern part of Siberia, inside the Arctic Circle. Vorkuta is a historically important city as it was formed by Stalin under the Soviet regime and was notorious for being one of the largest and deadliest prison camp complexes in the Soviet Union. This paper reveals insight into why and how Vorkuta functioned in the way that it did. Extensive memoirs, interviews with former Vorkuta prisoners, and secondary sources from historians and researchers provide the information used in this research paper. To understand the function of Vorkuta in the Soviet economy and society, one needs to look at the factors of inhospitable climate, geography, history, the value of coal, and urban growth. Vorkuta is an important city to study, because it exists today as a direct result of the GULAG system and forced labor under Stalin. The city of Vorkuta and the labor camps located there were a vital contribution to the Soviet economy as well as a convenient place to send the Soviet Union’s most feared political enemies.

Key Words: Vorkuta, GULAG, Stalin, Russia, coal

Just War is surely a fine thing – one does well for one’s self morally speaking by only waging Just Wars and only waging them justly. However, especially today, it seems to be that Just War is seen and spoken of as more than merely a moral code, especially in recent past. Instead it is taken as some form of agreed upon standard for behavior in war. Something extralegal but taken as accorded to by all. In this paper, as an ameliorative project, I will argue that Just Wars should be more than a moral standard, and should indeed be something extralegal accorded to by all. However, there is a major hurdle to be overcome; Just War cannot successfully be an accord as it is, especially in the context of the war on terror. First, I will explain what it takes for a war to be justly declared and justly waged. Next, I will briefly explain what an ameliorative project is, and clarify how this is one. Then, I will discuss my position on what we should want from Just War, and of which kind we want it to be. Thereafter, I will explore various barriers between the now and the desire for Just War. Finally, I will propose some ways we might go about bringing the doctrine we should want closer to being a reality.

Key Words: Applied Ethics, Just War, Animal Ethics

In a 2,500-person study, recruiting from 12 sites in 11 countries covering diverse intellectual and religious foundations, we find no cultural differences in individuals' ability to enjoy their thoughts when asked. While at home, participants were asked simply to either sit alone, thinking enjoyable thoughts, or to find something enjoyable to do by themselves. Participants generally found doing something relatively enjoyable, but found thinking a neutral to unpleasant activity. The pattern was constant across all sites, was unexplained by demographics or a set of individual difference measures, and a set of multilevel models showed that country-level differences were negligible. This finding builds on previous work demonstrating the surprising difficulty Americans have with prompted mental enjoyment (Wilson et al., 2014), and we conclude that, while thinking may be enjoyable at times, forcing yourself to think enjoyable thoughts is hard, and hard not just for WEIRD (White, Educated, from Industrialized, Rich Democracies) individuals.

Key Words: culture, thinking, mental control, hedonics

Gaining understanding plays a major role in our everyday thinking, enjoyment of art, scientific explanation, and much else. What is coming to understand? In §2, I discuss the view that one could not come to understand something without undergoing an experience with the content being understood (Bourget 2015). I suggest this view faces counterexamples. In §3, I discuss the view that one could not come to understand something without inferring what depends on what is being understood, or what one understands depends on (Grimm 2006). I suggest this view is true only vacuously, since we can easily identify dependencies throughout our mental states. Such problems lead me to propose my own metaphysical account of the process of coming to understand in §4. My view provides an explanatory necessary condition for coming to understand: one cannot come to understand something without a change in the concepts one uses to understand it.

Key Words: understanding, knowledge, conscious experience

Adults generally have a positive view of themselves and because of this tend to remember themselves in a positive way. It is unclear however, whether children, who are still developing an organized concept of who they are, are similarly influenced by their self-views. The current research focuses on how adults' and children's positive self-views influence their memory for their own good and bad deeds. As a first step to address this, I asked whether children and adults would have better memory for a behavior related to themselves if that behavior was nice, but not if the behavior was mean. Participants listened to a series of 30 verbs for nice behaviors (e.g., help, hug, greet) and 30 verbs for mean behaviors (e.g., hit, lie, spit). For each verb, they were asked to think about either how the behavior related to themselves (Self items: "Do you do this?") or how it related to an unfamiliar other person (Other items: "Does Fran do this?"). Afterwards, participants' memories for the verbs were tested. We found that both adults and children did remember the nice Self items better than the nice Other items. Importantly, they remembered the mean Self and Other items equally well. This provides preliminary evidence that as we initially form memories of our own behaviors, we may be more likely to form a lasting memory of our good deeds than our bad deeds.

Key Words: memory, self-concept, children

Action boundaries are, simply, the extents over which one can act. They are defined by the physical dimensions and fitness of an actor and the features of an environment, and they delineate the limits of one's ability to interact with the world. Our ability to successfully navigate the world would suggest that we know these boundaries, but a large body of literature – specifically about reaching ability - shows that people will over-estimate their body’s abilities when asked to explicitly estimate and report them. This inconsistency begs reconciliation, and in 3 studies this research found that while judgments of one’s reaching ability are consistently subject to this over-estimation bias (roughly 10%), reaching actions are not. When executing open-loop actions towards within-reach targets (actions with no visual feedback, with the eyes closed), participants will act in a way that indicates a much smaller bias to over-estimate (about 3%, rather than 10). In contrast, open-loop actions to beyond-reach targets will elicit responses that indicate the typical 10% over-estimation bias. In addition, participant response accuracy improved significantly and consistently across the 36 experimental trials even though they could never see what they were doing. This suggests that the proprioceptive information about the arm in space coupled with the remembered visual information about target location were sufficient to facilitate learning. To sum up: 1) your body knows what it can do, even if you can’t consciously report it, and 2) practice makes better, even with your eyes closed.

Key Words: Visual Perception, Cognition, Visually-Guided Action

In a classic demonstration of beliefs altering perception, individuals who experience the size-weight illusion invariably believe that the smaller of two equally-weighted items weighs more than the larger item. Since the discovery of the size-weight illusion in the 1700s, similar illusions such as the material-weight illusion and the color-weight illusion have been documented. These illusions arise from people’s expectations about the correspondence between object weight and some visually perceptible feature, such as size, material, or color. If people have strong expectations about associations between object value and weight, then weight estimates might be biased by value perception. In a series of studies, the weights of 6 vases that differed in aesthetics and perceived monetary value were made identical. After undergoing a priming procedure designed to evoke an association between value and weight, participants gave weight and value estimates of each of the vase. Preliminary results suggest participants rated vases they believed to be the most valuable as either the heaviest or the lightest, depending on how they were primed.

Key Words: Perception, Priming, Aesthetics, Value

Imposter Phenomenon (IP) is characterized by strong feelings of intellectual phoniness in high-achieving individuals (Clance & Imes, 1978). Underrepresented college students (i.e., ethnic/racial minority, first-generation, low-income) may be more susceptible to IP than their majority group counterparts (Ewing et. al, 2008). Given that IP is associated with negative psychosocial outcomes, identifying protective factors may be key to promoting healthy college adjustment (September et al., 2001). One such factor may be support from natural mentors. Natural mentors may help enhance students’ academic self-efficacy, enabling them to internalize positive feedback. The current study explores the ways natural mentors may attenuate IP over time for underrepresented students, via increases in academic self-efficacy. Participants in the current study included 340 underrepresented first year students (69% women) from a large public university. The age of participants ranged from 17 to 20 years of age (M = 18.11, SD = .37). Participants were assessed during the first (Time 1) and second (Time 2) semesters of their first year in college. Hierarchical regressions were run controlling for GPA, gender, and race. Number of natural mentors was negatively associated with IP. An additional hierarchical regression suggested natural mentors known through an academic context conferred greater benefit. Additionally, bootstrapped confidence intervals of indirect effects suggest mediation via increased academic self-efficacy. Results of the current study indicated greater number of natural mentoring relationships was associated with decreases in IP over time via increases in academic self-efficacy. Implications of these findings and directions for future research are discussed.

Key Words: Natural Mentors, Imposter Phenomenon, Underrepresented Students

I present a dynamic structural model of individual choice regarding high school education curricula, post-secondary education attainment, and early labor market opportunities. I estimate the model to investigate the returns to education from different types of U.S. high school curricula, with a particular focus on vocational education for non-college bound students, using panel data on students’ high school course selection and labor market outcomes from the Education Longitudinal Study of 2002. I account for high school curriculum self-selection by including instruments for high school vocational and academic opportunities along with local labor market controls, in addition to estimating the distribution of unobserved heterogeneity across individuals based on individual choice paths. The results show that trade vocational courses improve a non-college bound student’s later labor market wages and chance of being employed in a skilled occupation, while business vocational courses improve wages in low wage / high non-pecuniary utility occupations, relative to general education courses. Policy simulations suggest that incorporating vocational certification into high school vocational curricula would cause more students to take vocational courses and improve their labor market outcomes; that instituting a German-style high school tracking system in the United States would improve student education and labor market outcomes at the expense of student non-pecuniary utility in high school; and that providing free tuition to community college would cause more students to take general education curricula, increase graduation from community colleges, decrease the number of individuals in unskilled labor occupations, and slightly decrease graduation from 4-year colleges and universities.

Key Words: Education, Labor Market, Vocational

Despite efforts to increase diversity in higher education, social disparities persist; students from lower-socioeconomic status (SES) underperform and are less likely to graduate relative to their high-SES peers. Previous work has documented social factors that promote (or impede) stigmatized students’ sense of belonging and academic performance. In the present work, we take a different approach, examining how public space—a physical factor—might contribute to these disparities. Specifically, we test whether real and perceived restrictions on the use of public space contribute to SES disparities in students’ sense of belonging. We found that, relative to high-SES students, lower-SES students perceived public spaces on campus as more restricted. Moreover, we found that changing lower-SES students’ perceptions of the “publicness” of these spaces increased their sense of belonging at the University. Taken together, these studies demonstrate the importance of public spaces and suggest one way in which SES disparities might be reduced.

Key Words: social disparities, social class, sense of belonging, public space

The role of organizing and expansion is central to the study of social movements. It is the key point in trying to understand what leads to the emergence of collective, contentious action. Noting the importance of student activists in growing any movement, this paper explores what might lead college students to participate in activist groups on their respective campuses. The role of political opportunity structures and resource mobilization has been a consistent topic of discussion amongst social movements scholars for quite some time. Much of this previous focus however has been on the role of political connections or political strategy and the mobilization of economic capital towards movement claims. More recent work however has advocated for a more general field theory that introduces a particularly Bourdieusian perspective to understanding collective action. This paper looks to continue this train of thought by looking at the role of biographical availabilities, social capital and embeddedness among college students with aims at comparing those who participate in activist organizations and events as apposed to their contemporaries who choose to remain on the sidelines. Employing an original dataset of recent college graduates, this paper finds that those who participate in student activism tend to be involved in more groups, political and otherwise, and are, on average, more likely to spend more time and resources on their respective group. Following these outcomes, a necessary discussion emerges regarding the connected nature of biographical availabilities as a lack of constraint, the presence of specific forms of capital, and one’s position within intersecting strategic action fields

Key Words: Social Movements/Collective Action, Political Sociology, Inequality, Higher Education

Children’s lives are increasingly entwined with mobile technology, particularly within education. Yet educational mobile technology faces a critical problem: a lack of rigorous comparison between apps and the materials they aim to replicate or enhance. To address this, our research compares a traditional puzzle map of Australia to iWorldGeography – Australia, an app version of this puzzle. Study 1 tested learning of Australia’s state names in 32 five-year-olds randomly assigned to puzzle (N = 16) and app (N = 16) conditions. In the puzzle condition, children were given a hands-on lesson on the states (adapted from a school curriculum) by an experimenter and then allowed to play with the puzzle alone for ten minutes. In the app condition, children were introduced to the app by an experimenter and then allowed to play with the app alone for twenty minutes. Afterwards they were tested for recognition and recall of the states. Children in the puzzle condition learned significantly more states than children in the app condition on both recognition, t(30) = 3.32, p = .002, and recall tests, t(30) = 2.036, p = .05. Further research is examining learning over a longer time span. This research provides a crucial investigation of the differences between learning from mobile technology and learning from traditional, hands-on materials.

Key Words: media, learning, touchscreens, educational apps

Each year thousands of people must pass standardized exams to be certified in medical, legal, clinical, and technological fields. Unfortunately, the increasing number of examinees taking such tests has been accompanied by an increase in the instances of reported cheating and the invention of more sophisticated cheating techniques. The stealing and sharing of proprietary test content, such as the recording of items then leaking them, represents a significant threat to the integrity of testing. The purpose of the present study was to detect these compromised items using a combination of measurement models common in education and psychology and automated processes from the field of machine learning. We investigated an international healthcare certification exam (N = 13,584) with items that were compromised through screenshots or notes. The automated process attempted to learn how to detect compromised items using a combination of item properties. We will discuss the results in terms of which item properties were most important in identifying compromised items and the overall accuracy of our models.

Key Words: cheating, test security, psychometrics, item analysis

A lot of casual readers don't like--or are afraid of--Herman Melville's Moby-Dick. They think it has too much information about whales, that it lacks narrative coherence, that it's really just altogether too much going on about whales. But that totalizing nature of the book--and all the messiness that comes along with it--is essential to Melville's project. The book asks more questions than it answers; it fundamentally confronts and accepts its own inability to conclude anything. Much of the problem facing Ishmael, the book's narrator, and Ahab, its maniacal captain, is the difficulty of confronting a world that cannot be understood. Scholars of Moby-Dick usually pit Ishmael and Ahab against each other as opposites, but they are actually very similar in their recognition of the essential ambiguity of the world. That similarity is notable even in their language: Both use the word "some" frequently, as if to admit that there is something they cannot confront accurately in words but nonetheless need to denote. I examine their shared diction, as well as other similarities in their reaction to the great offense that is Moby Dick, to conclude that there is no static critical approach to Moby-Dick that is adequate to the book, that any proper reader ought to consider the same problems that plague the book's characters, that to read Moby-Dick to find or craft arguments is to misread.

Key Words: ambiguity, skepticism, epistemology, Moby-Dick

After winning the Noble Prize in Physics in 1921, Albert Einstein exclaimed, “If you ask in whom I am most interested at present, I must answer Dostoevsky--Dostoevsky gives me more than any scientist, more than Gauss!” Historian Alexander Vucinich posits that Einstein derived insights from readings of Dostoevsky that contributed to his formulation of the photoelectric effect and the theory of general relativity. What ideas did Einstein glean from Dostoevsky, and where did the novelist encounter the mathematical discourses appearing in his published works? Prior to becoming a man of letters, F.M. Dostoevsky (1821-1881) studied at the Main Engineering School in St. Petersburg from 1838 to 1843. In the context of nineteenth-century Russian literature, he is perhaps the only major novelist to have embedded explicit mathematical expressions and terminology in his prose. His works, for example, contain references to “square roots”, “logarithmic tables”, “repeating decimals”, and the curious equation, “2+2=5.” When Dostoevsky was arrested, submitted to mock execution by firing squad, and exiled to Siberia in 1849, his school notebooks were confiscated and destroyed by the Third Section of the Russian Secret Police. My project attempts to reconstruct the materials that Dostoevsky encountered during his education, and to trace their connection to his literary works. Whereas biographers tend to discount his studies, my project presents his education as a formative experience of his artistic development. The genius of Dostoevsky can be interpreted through a new lens that aligns his creative insights with the foundational frameworks of modern mathematics.

Key Words: F.M. Dostoevsky, Engineering Education in Imperial Russia, History of Mathematics

In 1957, Miles Davis made cinema soundtrack history. While watching a film clip of actress Jeanne Moreau wandering forlornly through Paris in Louis Malle’s Ascenseur pour l’echafaud (1958), Davis translated his reactions into trumpet improvisations, ultimately creating the film’s soundtrack. Improvised soundtrack production has been extremely rare. I argue that the primary reason for this marginalization is the film industry’s ideological and economic risk-averseness. Improvised scores are non-traditional; they are not carefully composed, but rather spontaneously performed in reaction to the film itself. They can be unpredictable, and thus risky for filmmakers who seek to maintain strict control over soundtrack production. That said, recent cinema boasts a few examples of jazz artists performing improvised scores. These include drummer Antonio Sanchez’ soundtrack for Alejandro González Iñárritu’s Birdman (2014), and trumpeter Mark Isham’s soundtrack for Alan Rudolph’s Afterglow (1997). I examine the production of these unique scores, read against the concept of risk aversion within the commercial film industry. I illustrate how these examples challenge traditional film-scoring conventions, connecting these subversions with the directors’ own distinctive industry statuses. These “maverick” directors operate outside film industry conventions in service of their own innovative aesthetic interests, resulting in their increased willingness to take risks. Such risk-taking includes offering creative (improvisational) liberties to jazz performers that extend beyond those typically afforded to the majority of film scorers. In highlighting these unique jazz improvisation/film intersections, I seek to generate further critical dialogue regarding innovative musical freedom within labor expectation in cultural industry work.

Key Words: jazz, film, improvisation, risk

This study describes the analysis and translation of image information into sound for acoustic music composition. Historically, the analysis of sonographic information for music composition started in 1970 with composers Gerard Grisey and Tristan Murail analyzing acoustic instruments spectra. This allowed them to understand how the sound changed or evolved through time. Understanding sound visually using a sonogram are a concept digital artists such as Ryoji Ikeda, Aphex Twin and Venetian Snares use in parts of their music. These artists used a picture and synthesized it into sound and used the sound for electronic music. My focus is the translation of images to sound and the analysis of musical features of the resulting sound for acoustic music composition. For image to sound translation, I wrote my own software that utilizes digital signal processing and image manipulation techniques that allow the user to translate an image into sound, alter the image and hear the results back immediately. After the sound is generated, the spectrum is analyzed for frequency content, spectral flux, centroid, loudness and noise. Finally, using the data extracted, I structure the form of the music using the properties interpolated from the image.

Key Words: Sound, Image, Sonification

This presentation is derived from my master's thesis, "Dark Ecology and Nineteenth Century Fiction," which studies the advent of dark ecology in the literature of this period. In this presentation, I will discuss the way that dark ecology, with a specific emphasis on the concept of hyperobjects, changes the way that we think about both language and social organization in Wuthering Heights and Jude the Obscure. These texts appear in different parts of the nineteenth century and suggest an evolution in thought throughout this brief period of less than fifty years. I argue that, when we think about language and social organization as hyperobjects, we see them as objects that are not only accessible to humans but as things that exist in a wider space that is accessible to all other beings in the universe. In literature, these hyperobjects manifest in various ways and reveal the ways that people of the nineteenth century were thinking about animals and the environment as well as themselves. This evolution in thought, I hope to suggest, is critical to the way that we think about humans, animals, and the environment today and in order to effectively study our own outlook on the universe, we must consider the origins of our contemporary thought.

Key Words: Dark Ecology, Thomas Hardy, Charlotte Bronte, Literary Studies, Victorian Studies

In 1950, to California poultry breeder Charles Vantress was awarded $5,000 by organizers of the “Chicken of Tomorrow Contest.” The competition, funded by the USDA, the University of Arkansas, and the Great Atlantic and Pacific Tea Company, American’s largest retailer, had begun three years earlier with the intention of creating a chicken tailored to mass-marketing. Vantress’ bird matured quickly and had qualities, like plump meaty breasts, that appealed to housewives struggling to feed growing families. Quickly, the chicken became the industry standard, accounting for nearly eighty percent of the global poultry population by the end of the century. This chapter from my dissertation, ““Farm to Table: The Supermarket Industry and the Transformation of American Agriculture, 1920-1990,” uses the Vantress chicken and the poultry industry more broadly to describe how corporate ingenuity and scientific innovation wrought an immense transformation in agricultural production during the latter half of the twentieth century. Chickens were the most significant of an entire class of products, such as tomatoes and soybeans, that had their biological nature altered to fit the needs of a population increasingly accustomed to a style of eating embodied by the logic of the supermarket –– fast, affordable, and always available regardless of season. The scientific intervention in poultry’s genetics was accompanied by an equally dramatic reconfiguration of rural labor that saw farmers join factory workers as cogs in a tightly-integrated system of corporate food processing and production that created jobs which paid little and pushed workers to their physical limits as a part of the relentless drive to keep costs low.

Key Words: Consumerism, Bioengineering, Agriculture

A diverse array of actin filament networks form and function to execute cellular processes and behaviors, but the mechanisms that coordinate the spatiotemporal organization and function of these networks are unknown. We previously identified the large GTPase, dynamin2 (dyn2), as an actin filament-remodeling factor that influences the architecture of filaments within dendritic lamellipodial actin networks and in contractile arrays of lamella (Mooren et al., 2009; Menon et al., 2014). Specifically, dyn2 specified the spatiotemporal distribution of α-actinin within lamellipodial F-actin networks in U2-OS cells. We now find using super-resolution imaging that dyn2 promotes formation of large clusters of α-actinin within lamellipodia that likely represent cross-linked actin filaments. The objective of this study is to determine the mechanism of dyn2-dependent F-actin remodeling leading to filament cross-linking. We hypothesize that dyn2, which is enriched at the distal edge of lamellipodia, is targeted to nascent F-actin junctions formed by Arp2/3 complex and cortactin to stabilize short, cross-linked actin filaments that are subsequently bound by α-actinin. To test this hypothesis, we determined the effects of dyn2 on formation of dendritic F-actin networks in vitro. Dyn2 inhibited the rate of actin polymerization nucleated by Arp2/3 complex and decreased filament branch density. Inhibition of actin assembly depended on cortactin, the ability of dyn2 to form oligomers and was enhanced in presence of both GTP and non-hydrolysable GTP analogs. In addition, cortactin, but not a mutant form of cortactin that does not bind dyn2, promoted formation of dyn2 oligomers. We conclude that oligomers of dyn2 in complex with cortactin regulate de novo actin nucleation by Arp2/3 complex. Future experiments will examine how dyn2 influences filament cross-linking.

Key Words: actin, dynamin, actin networks, actin remodeling, actin cytoskeleton, lamellipodia

Protein trafficking is essential to the health of every cell, and this holds especially true for neurons because of their elaborate processes and polarization. Due to their cellular complexity, neurons have acquired special endosomal machinery to deal with protein trafficking. One example of this specialized machinery is the protein Neuron enriched endosomal protein of 21kD (Neep21). Neep21 is involved in the trafficking of many proteins including GluR2, βAPP, and neurotensin receptor 1. Our lab has recently shown that Neep21 is involved in the axonal localization of the cell adhesion protein L1/NgCAM. While L1/NgCAM is only found on the axon, our lab discovered that in order to get to the axon it must first be delivered to the somatodendritic region where it is re-endocytosed and trafficked to the axon. This process, termed transcytosis, is dependent on Neep21. When Neep21 is knocked down, L1/NgCAM incorrectly accumulates on the somatodendritic region and is prematurely degraded in the lysosome. Another protein that undergoes both transcytosis and lysosomal evasion is the neurotrophin receptor TrkA, which is critical to the survival of sympathetic neurons during development. TrkA undergoes undergo multiple different trafficking events during its lifetime on its way to and from the distal axon, as well as into the dendrites. Preliminary data show that Neep21 is associated with TrkA-positive endosomes, therefore we sought to investigate when TrkA associates with Neep21 during its lifetime and if there is any functional loss of NGF signaling in the absence of Neep21.

Key Words: neurodevelopment, cell biology, protein trafficking, endosomes, neuroscience

Plasmodium falciparum, which causes the most severe form of malaria and a majority of deaths, has developed resistance to every drug intervention used thus far. Both single-nucleotide polymorphisms and copy number variations confer resistance in P. falciparum. Our lab studies a model in which parasites resistant to a novel antimalarial, DSM1, harbor multiple copies of regions of their genome including the gene target (Guler, Freeman et al. 2013). Each independent clone from this resistance model maintains unique amplified DNA regions (amplicons), displaying the chaotic nature of the initial steps of amplicon generation. In all cases, sequence at the boundaries of amplicons contain long stretches of monomeric adenines (A) or thymines (T). In the absence of significant homology to trigger homologous recombination, these A/T tracts likely provide the microhomology required for repairing DNA double-stranded breaks. Such DNA lesions are often created by complex chromosomal architecture and alternate DNA forms including hairpins. Our recent work has detected hairpins in close proximity to amplicon breakpoints, indicating that these sites may be the initial event that leads to amplification of beneficial genomic regions and subsequent drug resistance. Additionally, long A/T tracts are overrepresented and found in closer proximity to strong hairpins in a parasite clone prone to developing resistance. This finding provides predictions for genome locations that are prone to recombination and thereby development of drug resistance. Future work will include confirming these predictions on a genome-wide scale as well as investigating the prevalence of copy number variations between individual parasites.

Key Words: malaria, genetics, drug resistance

Background: Dementia will be one of the top ten causes of deaths in the world regardless of race, sex, and age. Caring for a demented family member puts the caregiver at great risk for depression. Yet, experts have not decided on what type of intervention has promising effects on depression. The aims of this review are to summarize experimental studies, and to provide grades of recommendations for treatment categories. Methods: Search strategy MEDLINE (Ovid), CINAHL, and PsycINFO electronic databases were searched. Key words were “caregiving” and “dementia”, using the search year from 1999 to 2014. Experimental studies were identified; only depression outcome trials were included. Methodological Quality Assessment This systematic review evaluated all included studies for risk of bias in order to appraise their methodological quality. Lastly, each treatment category of intervention was then given an overall grade of recommendation (GR) ranging. Results: Fifteen experimental studies, including nine RCTs and six quasi-experimental trials were analyzed. Two treatments out of five categories (cognitive-behavior therapy [CBT], multi-component intervention, counseling, education, and other) acquired high level of grade recommendation. (1) CBT acquired GR A given that three RCTs with significant effect on depression had 1+ level of evidence and (2) Counseling acquired GR B given that 1+ RCT and 2++ quasi-experimental trials. Conclusion: CBT that focused on applying practical skills offered excellent benefits in improving depression amongst caregivers. Future studies that test the efficacy of CBT in diverse ethnic groups and in underrepresented caregiver groups will enhance the generalizability of the interventions.

Key Words: Caregiver, Depression, Cognitive-Behavioral therapy, systematic review

Adontosternarchus is a species of weakly electric fish endemic to South America. These fish are able to communicate and navigate by generating an electric field via electric organ discharge (EOD). An interesting phenomena related to EOD is the active phase coupling behavior that can arise when a fish encounters a foreign electric field. In this scenario, the fish raises the frequency of it’s EOD and subsequently locks into the phase of the novel field. While other EOD behaviors such as the jamming avoidance response have been studied and well documented in other closely related species of Gymnotiform fish, the mechanisms behind active phase coupling remain largely unknown in Adontosternarchus. We know that weakly electric fishes in general use both phase and amplitude information to modify EOD’s, however, these sensory cues are a mystery in Adontosternarchus. We investigate this by presenting a stimulus signal to the fish and observing where the phase locking behavior occurs and if this behavior changes in response to different frequencies. We support this by investigating if the behavior is consistent with a model representing amplitude only-dependent phase coupling. Our findings show that active phase coupling in Adontosternarchus solely relies on amplitude information, revealing physiological explanations for a previously unknown phenomenon.

Key Words: Neurobiology, behavior, fish

Background: Sepsis induced acute kidney injury (AKI) is a common cause of death. Sepsis is associated with hypoferremia, to limit iron availability to pathogens and reduce iron-mediated oxidative stress. It has been shown that hypoferremia is due to hepcidin-induced degradation of ferroportin. We hypothesized that hepcidin would mitigate bacterial endotoxin-induced AKI. Methods: C57BL/6 were treated with saline or 50 μg of hepcidin, 24 hours prior to LPS (Escherichia coli O111:B4) injection (6.5 mg/kg). Renal function, injury and inflammatory markers were examined for up to 24 hours after LPS. Inner medullary collecting duct cells (iMCD3) were treated with 5% serum from different groups for 4-18 hours and analyzed for iNOS. The generation of ROS/RNS and serum cytotoxicity were measured using 123 dihydrorhodamine color transition test and LDH release respectively. Results: Kidney function (serum BUN) significantly declined 2 hours after LPS injection and progressively deteriorated for 24 hours. This was prevented by hepcidin treatment. Renal NGAL expression paralleled the changes in kidney function. Hepcidin treatment also reduced systemic TNF alpha and IL-6 production following LPS injection. The ultra-structure of the glomeruli revealed extensive loss of endothelial fenestrae and epithelial mitochondria in LPS treated mice, which was prevented by hepcidin treatment. In vitro studies demonstrated that serum from hepcidin + LPS mice induced less ROS/RNS release and cytotoxicity in iMCD3 cells compared to serum from LPS only mice. Conclusion: Our results demonstrate a protective role of hepcidin in endotoxin-mediated AKI, which is largely exerted through down regulation of systemic inflammation.

Key Words: acute kidney injury, sepsis, hepcidin, kidney, iron

NanoRNAs are small RNA molecules between 2 to ~ 6 nucleotides in length, which can prime transcription initiation in vivo. Abortive transcription initiation, backtracked transcription elongation and RNA degradation are some cellular processes which generate nanoRNA in cells which are then degraded by oligoribonuclease (Orn) or Orn homologs. Based on protein sequence similarity, a putative homolog of Orn has been detected in Thermotoga maritima (Tma), an early-branching anaerobic thermophile. Identification and characterization of Tma Orn will broaden our understanding of nanoRNA regulation in ancient bacteria. The recombinant Tma Orn has been successfully cloned, expressed and purified from E.coli. Based on our preliminary studies, Tma Orn degrades nanoRNAs that are 5 nt long in which the degradation is significantly enhance by the presence of divalent metal cation, manganese (Mn2+). Since RNA chaperone, host factor qβ (Hfq) is known to interact with many proteins and enzymes involved in RNA metabolism, we are investigating potential interactions between Tma Orn and Tma Hfq homolog using biochemical and biophysical techniques.

Key Words: NanoRNA, oligoribonuclease (Orn), Thermotoga maritima (Tma)

Myoendothelial junctions (MEJ) are projections from endothelial cells (EC) that make contact with neighboring smooth muscle cells (SMC) and are the anatomical hallmarks of resistance arteries. MEJ also exhibit presence of endoplasmic reticulum (ER), as evidenced from the ER retention signal –KDEL immunostaining and the live ER tracker (glibenclamide) in holes of the internal elastic lamina. Within the ER, calreticulin is a calcium binding protein that can bind approximately 50% of ER calcium and we found it was significantly enriched in the non lipid-raft fraction of the MEJ in vitro. Due to the importance of ER calcium signals at the MEJ in controlling vascular tone, we investigated the in vivo role of calreticulin in the endothelium and the MEJ. We generated a tamoxifen inducible, endothelial specific calreticulin floxed mouse.In these mice, we could not identify any basal change in blood pressure as measured by radiotelemetry. However, after acute injection of 0.1mg/kg phenylephrine, the rapid and significant increase in blood pressure seen in control mice was significantly blunted in mice lacking EC calreticulin. Because of this, we used pressure myography on isolated mesenteric arteries with less EC calreticulin and found them to have less constriction to PE dose response curves. In order to determine if this blunted response is due to less agonist-induced ER calcium release, we also characterized calcium signals at MEJs of mesenteric arteries. In summary, calreticulin in the EC appears to play an important role in the regulation of vascular tone and blood pressure, possibly through its actions at the ER in MEJs. We hypothesize calreticulin’s presence at the MEJ may be to mediate ER calcium release and provide the negative feedback that occurs upon SMC stimulation with PE.

Key Words: endothelial cell, calcium, physiology, blood pressure, vascular tone

Proprioceptive sensory neurons (proprioceptors) provide the basis for the conscious representation of our body in space and in turn, are major modulators of movement. The development of the proprioceptive circuit critically depend on neurotrophin-3 (NT-3) for survival and axon growth. In other neurotrophin-dependent systems, neurotrophin-mediated construction (e.g. cell survival, axon growth) countermands tumor necrosis factor receptor superfamily members (TNFRsf)-mediated destruction (e.g. cell death, axon pruning). In this project, we sought to investigate if two TNFRSF members, p75NTR or TNFR1a, are involved in naturally-occurring destruction in the proprioceptive circuit. We find that TNFR1 and its ligand TNF function as destructive signals that are required for natural loss of proprioceptor cells. Additionally, TNFR1a-/- and TNF-/- animals hyperperform on the rotarod compared to WT. In contrast, we find that p75NTR is a survival signal, where loss of p75NTR results in a decrease in proprioceptor cell numbers, and p75NTR-/- animals hypoperform on the rotarod compared to WT. Mice with compound mutation in p75NTR and TNF have normal cell numbers and normal rotarod function, and suggests that p75NTR and TNFR1-TNF functionally antagonize one another in proprioceptive circuit formation. Collectively, these data identify a novel antagonism between p75NTR and TNFR1a-TNF and provides basis for further study into the development of the nervous system.

Key Words: neuroscience, sensory system, developmental biology

Axon degeneration contributes to developmental sculpting of the nervous system as well as most neurological pathologies. Here we examine the role of death receptor 6 (DR6) in promoting developmental- and injury-induced axon degeneration. We find that DR6 has a modest role in driving developmental degeneration but appears to be critical for injury-induced degeneration. We also demonstrate that calcium, secreted from injured axons, functions as an extrinsic factor, which coordinates axonal degeneration of neighbors in a DR6-dependent autocrine/paracrine manner. Finally, we examined the requirement of DR6 and a related receptor, p75NTR, in promoting nerve degeneration in vivo. Severed DR6-/- sciatic nerves displayed rescued axon degeneration and remyelination. Interestingly, p75NTR-/-;DR6-/- animals displayed rescue of both axon and myelin degeneration which is comparable to phenotypes observed in Sarm1-/- and Wlds mice. Taken together, these findings suggest novel axon autonomous and non-autonomous roles for DR6 and p75NTR in promoting and coordinating injury-induced degeneration.

Key Words: TNFR, Wallerian Degeneration, calcium

Neisseria gonorrhoeae and N. meningitides are human pathogens which infect millions each year and are becoming increasingly antibiotic resistant. These bacteria utilize opacity-associated (Opa) proteins to mediate bacterial uptake into non-phagocytic and phagocytic cells as a means of infection. Opa proteins primarily engage carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs), hijacking host cellular mechanisms to induce bacterial engulfment. The Opa family of proteins are outer membrane β-barrels with eight transmembrane strands and four extracellular loops. Opa proteins bind CEACAMs with high affinity and specificity, yet regions within these loops necessary for engagement are highly diverse in sequence among Opa variants. We aim to determine how structural disorder within receptor-interacting domains of Opa loops allows the heterogeneous proteins to specifically engage diverse CEACAM receptors. Overall loop dynamics of Opa60 were determined using CW-EPR and NMR relaxation data. Results indicate that Opa loops are dynamic on the nanosecond timescale in lipid and detergent environments. Such flexibility may enable transient structures and interactions within the loops to promote receptor engagement. A model of the Opa60-CEACAM1 binding complex will be determined using a hybrid Double Electron Electron Resonance (DEER) and molecular dynamics approach. DEER distances between Opa60 and CEACAM1 provide spatial restraints for µs MD simulations of the complex, and preliminary models will be presented. Elucidating the mechanism of Opa-receptor interactions will augment our understanding of the determinants promoting the entry of a foreign pathogenic body into non-phagocytic cells.

Key Words: EPR, protein dynamics, binding complex

Introduction: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is seen in 1.5% of the U.S. population. Catheter ablation has become a well-accepted management strategy for AF; however, failure of this therapy is common, with less than two-thirds of the patients treated remaining free of AF on long-term follow-up. Method(s): The specific aims for this sequential mixed methods, quasi-experimental, two-group (n = 12 intervention; n = 12 control) study are to: (1) examine the feasibility and acceptability of a Viniyoga intervention for individuals with AF; (2) test whether or not a 6-week Viniyoga intervention in persons (18 to 65 years) with paroxysmal or persistent AF prior to ablation will decrease AF symptoms, depression, anxiety, prevent early recurrence of atrial tachyarrhythmia, and improve overall health-related quality of life (HRQOL) during the 6-month post-ablation period, if these participants continue to practice yoga post-ablation for 50 minutes at least twice a week; and (3) capture the participants’ perceptions of HRQOL and experiences with yoga. At 6 months post ablation, six randomly selected participants from each of the two groups will be asked to participate in a 40- to 45-minute semi-structured interview to capture their perceptions about their HRQOL and, for the intervention group only, to capture their experiences with yoga. Thematic content analysis will be used to categorize the recurrent, or common, “themes” identified in these data. Changes in the effects of the intervention will be analyzed using separate multilevel models (for each dependent variable).

Key Words: Yoga, Atrial fibrillation, mixed methods research

The left atrium of the heart is a thin-walled muscular chamber that serves as a reservoir and pump for oxygenated blood returning from the lungs. Atrial fibrillation (AF) is a condition in which the atrium does not contract properly due to uncoordinated electrical signals misfiring across the muscle chamber. AF in patients greatly increases the risk of stroke. To treat AF, catheter ablation is often used to electrically isolate specific, misfiring regions by cauterizing the atrial muscle, which is then replaced by non-conducting scar. The general trend in ablation for AF has been to induce larger amounts of scar in the hopes of preventing AF recurrence; however, relatively little attention has been paid to the consequences of more aggressive ablation for mechanical function of the atrium. We used a coupled finite-element and circulation model of the atrium to simulate AF treatment with various ablation patterns to determine their effect on atrial function. In our model, an increase in scar volume led to a decrease in atrial pump function. To look at the effect of scar location, we identified the regional effect of three common scar patterns on function of the free walls of the atrium. Ablations that involve regions with the highest baseline regional motion reduced function more than ablations in regions with low baseline function. Our results suggest that cardiologists can preserve atrial function while treating AF by choosing ablation patterns strategically.

Key Words: cardiovascular, finite element modeling, atrial fibrillation

Carbon nanotube yarn microelectrodes (CNTYMEs) exhibit rapid and selective detection of dopamine with fast-scan cyclic voltammetry (FSCV), however, the sensitivity limits their application in vivo. In this study, we introduce laser treatment as a simple, reliable, and efficient approach to improve the sensitivity of CNTYMEs by three fold while maintaining high temporal resolution. Laser treatment increases surface area and oxygen containing functional groups on the surface, which provides more adsorption sites for dopamine than at unmodified CNTYMEs. Moreover, similar to unmodified CNTYMEs, dopamine signal at laser treated CNTYMEs barely dropped with increasing repetition frequency compared to a significant decrease at carbon fiber microelectrodes (CFMEs). This is presumably caused by the significantly larger surface roughness which would trap dopamine-o-quinone within each scan and amplify dopamine signal without influencing temporal resolution. In addition, CNTYMEs were applied as an in vivo sensor with FSCV for the first time and laser treated CNTYMEs maintained high dopamine sensitivity compared to CFMEs with an increased scan frequency of 50 Hz. CNTYMEs with laser treatment are advantageous of their easy fabrication, high reproducibility, and rapid in vivo measurement of dopamine with high sensitivity and fast electron transfer, which might be expected to be a potential alternative of CFMEs.

Key Words: Carbon Nanotube Yarn, Real-time Measurement, Neurotransmitters

Eurasian boreal forests represent half of the global boreal forest, constitute nearly a quarter of global forested area , and comprise a significant area for the exchange of carbon between the terrestrial biosphere and the atmosphere. During a forest disturbance, carbon is lost from the ecosystem. Of all the disturbances, wildfires release the greatest amount of carbon into the atmosphere. As atmospheric concentrations increase, along with the frequency, intensity and extent of wildfires, it is important to understand how current and potential future fire disturbance regimes may affect the role of the Eurasian boreal forest in the global carbon cycle through altering the light environment, regeneration and successional trajectories. Furthermore, alongside the initial release of carbon to the atmosphere during a disturbance, the longer-term changes in forest structure and composition will further determine the capacity of the ecosystem to sequester and store carbon. We present a new, spatially-explicit fire module DISTRUB-F for utilization in tandem with a spatially-explicit, individually-based gap dynamics model SIBBORK. DISTURB-F simulates the effect of forest fire on the boreal ecosystem, namely the mortality of all or some trees (loss of biomass) within the forested landscape. The output from this coupled simulation can be used to estimate carbon losses from the ecosystem as a result of fires of different sizes and intensities over the course of secondary succession (decades to centuries).

Key Words: boreal forest, fire

Reactive nitrogen is necessary for food production, but when it is lost to the environment, it creates a cascade of detrimental environmental impacts. Sustainable agriculture is often suggested as a possible strategy for minimizing the negative environmental impacts of modern agriculture. To evaluate the N losses from a Virginia permaculture livestock farm, our team 1) calculated a farm N budget for 2012-2015, 2) quantified the N fluxes in the surface waters and 3) evaluated the role of a pond in influencing these fluxes. Initial data estimate that the farm N inputs were greater than the farm N outputs; therefore there are unknown sinks totaling 30-40 kg N/ha/year or 80% of nitrogen inputs. On 60% of days sampled, dissolved inorganic N (DIN) flux into the farm via stream water was greater than DIN flux out of the farm via stream water; however, when averaged over a year, total DIN fluxes were similar. On 78% of days sampled, total N flux into the pond was greater than total N flux out of the pond; suggesting that during base flow conditions, the pond is an N sink. When compared to conventional livestock production, this permaculture farm loses less N per unit area and has lower N fluxes in the surface waters. With a deeper knowledge of the nitrogen fluxes and nitrogen management strategies on a permaculture livestock farm, researchers will be better equipped to determine the potential sustainability of alternative farming systems.

Key Words: nitrogen, agriculture, biogeochemistry, hydrology

Data that have group labels associated with individual observations allow for cluster analysis along multiple aspects of interest. When this analysis is desired at both individual and consolidated (group) levels of a given data set, failing to appropriately model the relationship between the parameters across these levels can lead to logically inconsistent parameter estimation. This research introduces a principled mixture-model based approach to a multi-level cluster analysis. Simultaneously, constraints on the bidirectional relationship between group and individual level cluster population parameters and a variety of constraints at the individual level may be imposed. One distinct advantage of this model based approach is that it allows for inferential questions to be asked regarding cluster membership due to the probabilistic nature of uncertainty in membership assignment. An additional benefit of this setting is that model selection becomes one of Bayesian model choice. This research allows for robust and logically consistent identification of unknown data structures and parameters of interest which can be useful in applied settings including political campaign, policy initiative, and NBA roster management strategies.

Key Words: Clustering, Constraint, Mixture-model

S-nitrosocompunds are of strong biochemical interest due to their role as nitric oxide donors and their potential role in cardiovascular and pulmonary signaling. To elucidate the role of S-NO in proteins, exact concentrations must be measured in healthy and diseased tissues and cells throughout the body. Further understanding would benefit from metabolic studies of S-NO groups utilizing isotopic labeling. Levels of S-NO groups in cell and organ systems are typically 10-1000 nM, however this number is not known exactly for many tissues due to the potential breaking or formation of these bonds during sample preparation. Currently the most sensitive technique available for S-NO detection, chemiluminescence, has a limit of detection of 50 nM. However, chemiluminescence has the significant drawback of lack of specificity between 14NO and 15NO, making the technique not viable for use in metabolic studies. With the current cavity ring down (CRDS) set up in the Lehmann lab limits of detection of 2 pico moles and 5 pico moles for 14NO and 15NO respectively, which corresponds to concentrations of 20-50 nM in a typical 100 microliter sample. Progress toward measuring S-NO groups in biological samples will be presented.

Key Words: spectroscopy, biological detection, nitric oxide

We have explored the dipole-dipole mediated, resonant energy transfer (RET) reaction, 32p3/2 + 32p3/2 → 32s + 33s, in an ensemble of cold 85Rb Rydberg atoms. Stark tuning is employed to measure the population transfer probability as a function of the total electronic energy difference between the initial and final atom-pair states over a range of Rydberg atom densities. The observed lineshapes provide information on the role of beyond nearest-neighbor interactions, the range of Rydberg atom separations, and the electric field inhomogeneity in the sample. The widths of the resonance lineshapes increase approximately linearly with the Rydberg density and are only a factor of two larger than expected for two-body, nearest-neighbor interactions alone. These results are in agreement with the prediction that beyond nearest-neighbor exchange interactions should not influence the population transfer process to the degree once thought. At low densities, Gaussian rather than Lorentzian lineshapes are observed due to electric field inhomogeneities, allowing us to set an upper limit for the field variation across the Rydberg sample. At higher densities, non-Lorentzian, cusp-like lineshapes characterized by sharp central peaks and broad wings reflect the random distribution of interatomic distances within the MOT. These lineshapes are well-reproduced by an analytic expression derived from a nearest-neighbor interaction model and may serve as a useful fingerprint for characterizing the position correlation function for atoms within the MOT.

Key Words: Rydberg atoms, laser cooling

The tungsten dearomatization agent of the form TpW(NO)(PMe3)(η2-benzene) has been shown to facilitate a wide range of reactivity pathways for aromatic compounds, upon coordination to the tungsten complex, leading to the isolation of novel organic compounds with complex molecular structures in relatively few synthetic steps. The current drawback to this method is that when these chiral molecules are synthesized, the product is formed as a 50:50 mixture of enantiomers due to the tungsten synthetic precursor existing as a racemic mixture. A practical procedure for the large-scale synthesis of an enantioenriched tungsten precursor has been developed in order to allow for the synthesis of chiral molecules in high enantiomeric excess. The coordination and functionalization of biologically interesting aromatic heterocycles, such as indoline, tetrahydroquinoline, and pyridine has led to the isolation of novel alkaloids, which are submitted to chemical libraries at Eli Lily and the NIH to be tested for biological activity. The use of an enantioenriched form of the tungsten synthetic precursor would enable the synthesis of enantiomerically enriched alkaloids, with the potential for pharmaceutical applications.

Key Words: dearomatization, enantiomeric excess, alkaloid

This study assessed qualities of adolescent romantic relationships as long-term predictors of mental health in adulthood. It utilized a longitudinal multi-method, multi-informant study of a community sample of 184 participants assessed annually from the ages of 13 to 27 years, along with their romantic partners at ages 16 through 18. Partner-reported conflict at age 17 predicted relative increases in internalizing and externalizing behaviors in adulthood at age 27. Teen engagement with their partner during a support-seeking task at age 17 predicted relative decreases in externalizing behaviors over time. Predictions remained after accounting for numerous potential confounds including relationship duration, seriousness, and intensity, adolescent anxious, depressive, and externalizing symptoms, adolescent family income, and gender. These findings have important implications for understanding the specific qualities within adolescent romantic relationships that have long-lasting impacts on adult psychological health.

Key Words: romantic relationships, adolescence, mental health, conflict, support

Research suggests a normative difference in brain activity between empathy for a friend and empathy for a stranger. But individual differences in empathy may be more prominent when observing a stranger’s physical pain. We investigated the association between levels of empathy and brain activity while anticipating an electric shock to a stranger. 25 individuals underwent functional magnetic resonance imaging (fMRI) while alone, holding a partner’s hand, or holding a stranger’s hand. During the scan, participants were presented with randomly-ordered threat and safety cues. Threat cues indicated a 20% chance of shock, and shocks were directed at partners and strangers at different times. Empathy was measured using the Balanced Emotional Empathy Scale (BEES). BEES scores were then used as a covariate in a mixed effects model to determine brain activity positively and negatively associated with empathy scores when holding the hands of friends and strangers who were threatened with electric shock. We found that lower self-reported empathy for strangers associated with higher brain activity in the paracingulate cortex when participants were anticipating electric shock to the stranger. Because the paracingulate cortex has been associated in previous empathy research with theory of mind processes, we speculate that people with lower trait empathy scores are more likely to rely on a theory or mind strategy when understanding the experience of a distressed stranger. By contrast, we speculate that empathizing with familiar friends may entail a more simulation based strategy.

Key Words: Empathy, fMRI, emotion, perspective taking

One of many ways to learn about the social world is through fictional media, such as books and television shows. Here, we investigated whether and how exposure to prosocial stories influences preschoolers’ prosocial behavior. We were specifically interested in the role of perspective-taking. Prosocial stories can be told from many perspectives, including the agent of the prosocial action (e.g., the person who shares), or the action’s recipient. Does the perspective from which the story is told influence subsequent behavior? Four- and 5-year-olds were read a short story from either a prosocial agent’s or a recipient’s perspective, and then completed assessments of prosocial behavior and empathy. Parent surveys evaluated children’s social skills. A comparison group of 5-year-olds completed these same assessments without reading a story beforehand, providing a baseline measure of children’s prosocial tendencies. To investigate whether home media viewing influenced the behaviors seen in lab, parents of the comparison group also tracked their children’s media exposure for one week. Story perspective (agent or recipient) did not impact children’s prosocial behavior. However, there was marginal improvement in empathic concern following storybook reading when compared to no reading, t(42) = 1.96, p = 0.057, Cohen’s d = 0.59, suggesting that prosocial storybooks may lead to immediate increases in preschoolers’ prosocial behavior regardless of the perspective from which they are told. Future research will attempt to strengthen children’s perspective-taking while reading to see if there are situations in which perspective does influence prosocial behavior.

Key Words: Perspective-Taking, Prosocial Behavior, Empathy, Storybooks, Media