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Primate Proteomic Composition Of Seminal Plasma And Prostate-Specific Transglutaminase Activity In Relation To Sexual Selection., Amanda M.C. Zielen
Primate Proteomic Composition Of Seminal Plasma And Prostate-Specific Transglutaminase Activity In Relation To Sexual Selection., Amanda M.C. Zielen
Electronic Theses and Dissertations
Humans (Homo sapiens), chimpanzees (Pan troglodytes), and gorillas (Gorilla gorilla) have diverse mating systems with varying levels of sperm competition. Several seminal plasma genes have been claimed to evolve under positive selection, while others are altered or lost. This study aims to identify biologically relevant differences among seminal plasma proteomes of primates in relation to mating systems and previous genomic studies. Seminal plasma from three individuals of each species were run in triplicate in shotgun liquid chromatography – tandem mass spectrometry (LC-MS/MS) and confirmed with Western blots. Over 7,000 peptides were identified across all …
Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan
Electronic Theses and Dissertations
This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.
The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …
Target Based Design And Synthesis Of Heterocycles In The Potential Treatment Of Cancer And Opportunistic Infection, Shruti Choudhary
Target Based Design And Synthesis Of Heterocycles In The Potential Treatment Of Cancer And Opportunistic Infection, Shruti Choudhary
Electronic Theses and Dissertations
Dose limiting toxicity and development of multidrug resistance by the tumors are the major limitations of current cancer chemotherapy. Microtubule targeting agents (MTAs) are a structurally diverse set of compounds that disrupt microtubule dynamics and exert their anticancer effect. Among the various classes of such agents, the colchicine site binding agents are particularly important as they circumvent the Pgp and β-III tubulin mediated clinical resistance. These resistance mechanisms, when manifested, are a major reason for the failure of clinically used agents such as taxanes and vinca alkaloids. A series of monocyclic pyrimidine analogs were designed and synthesized as colchicine site …
Modeling The Binding Of Neurotransmitter Transporter Inhibitors With Molecular Dynamics And Free Energy Calculations, Bernandie Jean
Modeling The Binding Of Neurotransmitter Transporter Inhibitors With Molecular Dynamics And Free Energy Calculations, Bernandie Jean
Electronic Theses and Dissertations
The monoamine transporter (MAT) proteins responsible for the reuptake of the neurotransmitter substrates, dopamine, serotonin, and norepinephrine, are drug targets for the treatment of psychiatric disorders including depression, anxiety, and attention deficit hyperactivity disorder. Small molecules that inhibit these proteins can serve as useful therapeutic agents. However, some dopamine transporter (DAT) inhibitors, such as cocaine and methamphetamine, are highly addictive and abusable. Efforts have been made to develop small molecules that will inhibit the transporters and elucidate specific binding site interactions. This work provides knowledge of molecular interactions associated with MAT inhibitors by offering an atomistic perspective that can guide …
Target Based Design And Synthesis Of Fused Pyrimidines In The Potential Treatment Of Cancer And Opportunistic Infection, Khushbu Shah
Target Based Design And Synthesis Of Fused Pyrimidines In The Potential Treatment Of Cancer And Opportunistic Infection, Khushbu Shah
Electronic Theses and Dissertations
This dissertation describes an introduction, background and research progress in the areas of agents designed as (a) selective Pneumocystis jirovecii dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection; (b) inhibitors of microtubule polymerization and multiple receptor tyrosine kinase (RTK) for potential treatment of cancer; and (c) substrates for tumor-targeted therapy for cancer.
PCP is a host species-specific infection. Most of the drugs, synthesized and evaluated so far, have been tested against Pneumocystis carinii dihydrofolate reductase (the causative organism in rats), which would not necessarily be effective against pjDHFR (the causative organism in humans). Trimethoprim-sulfamethoxazole (TMP-SMX) combination, which has been …
Nitric Oxide Release From Poly(Lactic-Co-Glycolic Acid) Nanoparticles And Titanium Alloy, Nina A. Reger
Nitric Oxide Release From Poly(Lactic-Co-Glycolic Acid) Nanoparticles And Titanium Alloy, Nina A. Reger
Electronic Theses and Dissertations
Current methods for the treatment of bacterial infection involve the use of systemic antibiotics, which are high concentrations of antibiotics delivered over a long period time. Unfortunately, the use of systemic antibiotics can cause harmful side effects to the patient and increases the possibility for antibiotic resistance. The delivery of antibiotics or alternative antimicrobial compounds, such as nitric oxide, directly to the site of infection would decrease the amount of antibiotic necessary to treat a bacterial infection.
Poly (lactic-co-glycolic acid)/polyvinyl alcohol nanoparticles and a titanium- aluminum-vanadium metal oxide alloy implant were surface functionalized to deliver nitric oxide. Polymer nanoparticles can …
Distribution Changes, Genetic Population Structure, And A Novel Environmental Dna (Edna) Detection Method For Darters (Subgenus Nothonotus) In The Upper Ohio River Watershed, Anthony S. Honick
Electronic Theses and Dissertations
In the upper Ohio River watershed three species of small-bodied benthic fish the Bluebreast Darter, Etheostoma (Nothonotus) camurum (Cope), the Tippecanoe Darter, Etheostoma (Nothonotus) tippecanoe Jordan and Evermann, and the Spotted Darter, Etheostoma (Nothonotus) maculatum Kirtland previously existed in disjunct distributions due to poor water quality and habitat degradation. Signs of recovery indicated that these species were moving from areas of refugia into the deeper mainstem waters of the Allegheny and Ohio rivers and expanding their distributions. To provide information for the proper conservation management of these species this dissertation was divided into three stages: 1) distribution records were updated …
Local Health Department Adoption Of Health Information Technology And Its Impact On Population Health, Tina Yeung
Local Health Department Adoption Of Health Information Technology And Its Impact On Population Health, Tina Yeung
Electronic Theses and Dissertations
Since the enactment of the HITECH Act in 2009, the US has invested billions in building a robust health information technology (HIT) infrastructure that is secure, capable of the electronic transfer of data and allows for real-time access of patient medical data, among others. This empirical study explored the driving forces (coercive, mimetic, and normative) in the adoption of HIT (i.e. EHRs and HIEs) by local health departments (LHDs) and how it has impacted the population health of counties in the US. The researcher conducted a cross-sectional, quantitative study using secondary data sources. The study included data on 505 local …
Improvement And Development Of Analytical Forensic Methods: Arson Investigation And Drug Detection In Fingerprints And Hair, Sarah Anne Glenn
Improvement And Development Of Analytical Forensic Methods: Arson Investigation And Drug Detection In Fingerprints And Hair, Sarah Anne Glenn
Electronic Theses and Dissertations
Forensic science is the cornerstone of criminal investigations. Due to the overexposure of forensic science in the media, the true nature of forensic science is often overlooked. Forensic science is a rigorous exacting science that applies methods developed in the wider scientific community to the analysis of evidence collected from crime scenes. As far back as the 6th century people were using forensics to solve crimes. Since then the science behind forensic science has increased exponentially with new methods being researched and developed. This research aims to address two of the larger subsections of forensic science, arson and drug detection. …
Responses Of The Ocellated Turkey (Meleagris Ocellata) To Human Disturbance, Thomas Hughes Martin
Responses Of The Ocellated Turkey (Meleagris Ocellata) To Human Disturbance, Thomas Hughes Martin
Electronic Theses and Dissertations
Habitat loss and habitat degradation are major drivers of the current biodiversity crisis. Nowhere else are these threats more severe than in the tropics. Because the tropics are estimated to contain as much as 60% of all the species on Earth, they are critically important for the conservation of biodiversity. To conserve species we need to understand both the factors that lead to extinction and how the taxa that persist are able to adapt to the rapid anthropogenic change of their environment. The Ocellated Turkey (Meleagris ocellata) is a Neotropical galliform bird of conservation concern because it faces a rapidly …
Leadership And Subordinate Engagement: A Meta-Analytic Examination Of Its Mechanisms Using Self-Determination Theory, Henry Young
Leadership And Subordinate Engagement: A Meta-Analytic Examination Of Its Mechanisms Using Self-Determination Theory, Henry Young
Electronic Theses and Dissertations
Although past research has suggested ineffective leadership to be the most common reason for low levels of employee engagement, little is known about the mediating mechanisms underlying this relationship. To address this gap in research, I tested a theoretical model based on Self-Determination Theory (SDT; Deci & Ryan, 2000) in which two focal mechanisms, leader-member exchange (LMX) and empowerment, functioned in sequential order to predict the relationship between Full Range Leadership and subordinate engagement. Results showed that transactional leadership had positive and negative indirect effects on engagement, suggesting that transactional leadership comprises a "double-edged sword" as a predictor of subordinate …
Local Transient Characterization Of Thermofluid Heat Transfer Coefficient At Solid-Liquid Nano-Interfaces, Mehrdad Mehrvand
Local Transient Characterization Of Thermofluid Heat Transfer Coefficient At Solid-Liquid Nano-Interfaces, Mehrdad Mehrvand
Electronic Theses and Dissertations
The demands for increasingly smaller, more capable, and higher power density technologies in microelectronics, energy, or aerospace systems have heightened the need for new methods to manage and characterize extreme heat fluxes (EHF). Microscale liquid cooling techniques are viewed as a promising solution for removing heat from high heat flux (HHF) systems. However, there have been challenges in physical understanding and predicting local thermal transport at the interface of micro and nanoscale structures/devices due to ballistic effects and complex coupling of mass, momentum, and energy transport at the solid-liquid-vapor interfaces over multiple time and length scales. Moreover, it's challenging to …
Quality By Design Procedure For Continuous Pharmaceutical Manufacturing: An Integrated Flowsheet Model Approach, Ashley Vezina
Quality By Design Procedure For Continuous Pharmaceutical Manufacturing: An Integrated Flowsheet Model Approach, Ashley Vezina
Electronic Theses and Dissertations
Pharmaceutical manufacturing is crucial to global healthcare and requires a higher, more consistent level of quality than any other industry. Yet, the traditional pharmaceutical batch manufacturing has remained largely unchanged in the last fifty years due to high R&D costs, shorter patent durations, and regulatory uncertainty. This has led regulatory bodies to promote modernization of manufacturing process to continuous pharmaceutical manufacturing (CPM) by introducing new methodologies including quality by design, design space, and process analytical technology (PAT). This represents a shift away from the traditional pharmaceutical manufacturing way of thinking towards a risk based approach that promotes increased product and …
Scientific Transformations: A Philosophical And Historical Analysis Of Cosmology From Copernicus To Newton, Manuel-Albert Castillo
Scientific Transformations: A Philosophical And Historical Analysis Of Cosmology From Copernicus To Newton, Manuel-Albert Castillo
Electronic Theses and Dissertations
The purpose of this thesis is to show a transformation around the scientific revolution from the sixteenth to seventeenth centuries against a Whig approach in which it still lingers in the history of science. I find the transformations of modern science through the cosmological models of Nicholas Copernicus, Johannes Kepler, Galileo Galilei and Isaac Newton. Since of the enormous content, I shall only pay particular attention to Copernicus and Newton in which the emerging sciences transformed the cosmos on what Alexandre Koyré calls from a "closed world to infinite universe". As an interdisciplinary approach, I used the methods and inquiries …
Cafeteria Culture: An Anthropological Approach To Lunchtime In A Central Florida Elementary School, Emily Herrington
Cafeteria Culture: An Anthropological Approach To Lunchtime In A Central Florida Elementary School, Emily Herrington
Electronic Theses and Dissertations
Public school cafeterias are used by nearly 51 million children (ages 4-17) in the United States every day. With over 40% of the approximately 73 million children (ages 0-17) participating in the National School Lunch Program (NSLP), public school lunches carry resounding nutritional, social, and educational significance for their consumers. This fact, coupled with frequent media attention to school lunch food, notwithstanding, a notable lack of social scientific engagement with both students' perspectives and NSLP operators persists. Divided into two studies, this research utilizes ethnographic methods to explore students' lunchtime experiences within a Central Florida public elementary school cafeteria. Both …
An Assessment Of Trace Elements Distribution In Teeth Utilizing A Sample Group From Postclassic Lamanai: The Application Of La-Icp-Ms In Bioarchaeology And Forensics, Michelle Hawkins
Electronic Theses and Dissertations
Trace element analysis of skeletal remains and teeth is a common research technique in biological and forensic anthropology. In particular, LA-ICP-MS has become a widely-accepted tool for analyzing and mapping the distribution of trace elements in teeth. Investigation into the relative spectral intensities and spatial distribution of thirteen trace isotopes (13C, 24Mg, 27Al, 31P, 44Ca, 47Ti, 52Cr, 55Mn, 56Fe, 66Zn, 88Sr, 138Ba, 208Pb) within teeth was undertaken using LA-ICP-MS. The total archaeological sample of teeth (N=26) was comprised of four tooth types (UCI, ULI, UPM1, and UPM2) and 18 individuals from a Postclassic Lamanai site. In preparation for analysis, teeth …
A Major Dna Double Strand Repair Pathway And Cancer-Associated Circulating Proteins Are Effecters Of Epigenetic Revision., Brittany Allen
A Major Dna Double Strand Repair Pathway And Cancer-Associated Circulating Proteins Are Effecters Of Epigenetic Revision., Brittany Allen
Electronic Theses and Dissertations
DNA methylation is a vital epigenetic process that acts as a major control mechanism for gene expression. In addition to its essential role in many normal cellular processes, it is also implicated in a wide variety of disease states and processes including cancer. Along with genetic mutations, aberrant DNA methylation patterns, specifically the inappropriate DNA methylation or demethylation of CpG residues, may activate oncogenes or suppress tumor suppressor genes, respectively. These changes can generate or facilitate the progression of tumorigenesis and tend to accumulate throughout the development of cancer. Although they play such a major role in cancer and in …
Plasma Dynamics Of Laser Filaments, Danielle Reyes
Plasma Dynamics Of Laser Filaments, Danielle Reyes
Electronic Theses and Dissertations
Laser filamentation is a complex phenomenon occurring for pulses with peak power above a critical value. A filament is a dynamic self-guided structure characterized by several unique qualities, which include a beam with a high-intensity core surrounded by an energy reservoir, a weakly ionized plasma channel, and supercontinuum generation. Several of the proposed applications for filamentation utilize the plasma channel, such as for assisted electric discharge and microwave guiding. However, filament properties are highly influenced by the physical conditions under which they are formed. A host of studies have been conducted to further characterize filaments, but much work still remains …
"Yeah I'M A Girl. I Play Video Games.": Identity Work Of Collegiate Women Gamers, Emily Rosenbaum
"Yeah I'M A Girl. I Play Video Games.": Identity Work Of Collegiate Women Gamers, Emily Rosenbaum
Electronic Theses and Dissertations
Despite accounting for almost half of the game playing population, women gamers are an underrepresented and excluded group within the gaming culture, both in regards to the advertising and production of video games. Prior research suggests that male gamers exclude women from gaming activities, question their legitimacy within the community, and create hostile environments for women both virtually in-game and in physical gaming spaces. As such, women gamers can be understood to hold a marginalized status with the gaming community. The current study looks to examine how women define themselves as "gamers" while negotiating this marginalized status. By adopting an …
Computational Fluid Dynamics Study Of Thromboembolism As A Function Of Shunt Size And Placement In The Hybrid Norwood Palliative Treatment Of Hypoplastic Left Heart Syndrome, John Seligson
Electronic Theses and Dissertations
The Hybrid Norwood procedure has emerged as a promising alternative palliative first stage treatment for infants with Hypoplastic Left Heart Syndrome (HLHS). The procedure is done to provide necessary blood flow to the pulmonary and systemic regions of the body. The procedure can affect hemodynamic conditions to be pro-thrombotic, and thrombus particles can form and release from the vessel walls and enter the flow. Assuming these particles are formed and released from the shunt surface, a Computational Fluid Dynamics (CFD) model can be used to mimic the patient's vasculature geometry and predict the occurrence of embolization to the carotid or …
Advanced Castes At The Outset Of Eusociality In Wasps (Vespidae), Patrick Piekarski
Advanced Castes At The Outset Of Eusociality In Wasps (Vespidae), Patrick Piekarski
Electronic Theses and Dissertations
A dominating and widespread view is that evolutionary change is gradual and waits upon mutation. Likewise, it is thought that workers and queens of eusocial insects diverged gradually and stepwise. That is, rudimentary castes preceded advanced castes. This paradigm hinges on eusociality having evolved once in Vespidae, and primitively eusocial paper wasps lacking ontogenetic caste biasing (differentiation of castes during larval development). Using a phylogenomic approach this study shows strong evidence for two origins of eusociality in vespid wasps, wherein one origin is likely characterized by the sudden appearance of castes with physiological, and perhaps even morphological, differences established before …
Assessment Of Physical Workload, Ergonomic Problems And Prevalence Of Pain Among Low Wage Hotel Housekeepers In Orlando, Rachel Mammen
Assessment Of Physical Workload, Ergonomic Problems And Prevalence Of Pain Among Low Wage Hotel Housekeepers In Orlando, Rachel Mammen
Electronic Theses and Dissertations
This research study examined the work conditions, ergonomic problems, and prevalence of pain among low wage hotel room cleaners in Orlando. In most hotels, the cleanliness of guestrooms is one of the most important service standards expected by customers. The role of the housekeeper is thus critical to service provision and hotel profitability. The hospitality industry is a major recruiter of low wage workers with the majority working in housekeeping departments. Due to the nature of the research problem, a positivist quantitative approach was adopted although the survey instrument included space for qualitative comments to some of the latter open-ended …
Mesoscopic Interactions In Complex Photonic Media, Roxana Rezvani Naraghi
Mesoscopic Interactions In Complex Photonic Media, Roxana Rezvani Naraghi
Electronic Theses and Dissertations
Mesoscale optics provides a framework for understanding a wide range of phenomena occurring in a variety of fields ranging from biological tissues to composite materials and from colloidal physics to fabricated nanostructures. When light interacts with a complex system, the outcome depends significantly on the length and time scales of interaction. Mesoscale optics offers the apparatus necessary for describing specific manifestations of wave phenomena such as interference and phase memory in complex media. In-depth understanding of mesoscale phenomena provides the required quantitative explanations that neither microscopic nor macroscopic models of light-matter interaction can afford. Modeling mesoscopic systems is challenging because …
Posttraumatic Stress Disorder Or Combat Experience? A Functional Near-Infrared Spectroscopy Study Of Trauma-Related Auditory And Olfactory Cues, Michael Gramlich
Posttraumatic Stress Disorder Or Combat Experience? A Functional Near-Infrared Spectroscopy Study Of Trauma-Related Auditory And Olfactory Cues, Michael Gramlich
Electronic Theses and Dissertations
While the clinical communities are aware of the prevalence of posttraumatic stress disorder (PTSD) among OEF/OIF/OND veterans, further efforts are necessary to bolster comprehensive strategies for assessment and treatment. The purpose of this study was to investigate whether a combat-related PTSD symptom provocation paradigm would elicit unique neurological responses via functional near-infrared spectroscopy across three groups – combat veterans with PTSD, combat veterans without PTSD, and nonmilitary participants without PTSD. Results indicated that combat veterans with PTSD demonstrated significant activation during exposure to a trauma-related sound compared to nonmilitary personnel at channels 14 (d = 1.03) and 15 (d = …
Effects Of An Acute High-Volume Isokinetic Intervention On Inflammatory And Strength Changes: Influence Of Age, Joseph Gordon
Effects Of An Acute High-Volume Isokinetic Intervention On Inflammatory And Strength Changes: Influence Of Age, Joseph Gordon
Electronic Theses and Dissertations
PURPOSE: The purpose of this study was to compare the effects of a high volume isokinetic intervention on lower body strength and inflammation, as well as markers of muscle damage in the subsequent 48 hours between younger and middle-aged men. METHODS: 19 healthy, recreationally trained men were randomly assigned to two groups, younger adults (YA: 21.8 ± 2.0 y; 90.7 ± 11.6 kg; 21.5 ± 4.1 % body fat), or middle-aged adults (MA: 47.0 ± 4.4 y; 96.0 ± 21.5; 24.8 ± 6.3 % body fat). Both groups reported to the human performance laboratory (HPL) on four separate occasions. On …
An Anthropological Study Of Eating Perspectives, Meal Composition, And Food Choices Among Diverse Student Populations, Chelsea Daws
An Anthropological Study Of Eating Perspectives, Meal Composition, And Food Choices Among Diverse Student Populations, Chelsea Daws
Electronic Theses and Dissertations
My thesis explores the factors that shape or reinforce international college students' perceptions of food. This research not only examines how cultural values affect individual nutrition and maintenance of eating behaviors, it also addresses the extent to which accessibility impacts eating behaviors. Notably, the research endeavor uses the concept of dietary habitus as an underlying directive mechanism for study. This study finds that most students experience a reduction in their fruit and vegetable intake. Another finding suggests that international students eat healthier and are more structured in comparison to domestic students if they hybridize their dietary habitus. Research findings also …
Probation Officer Productivity: Using The Effort-Reward Imbalance Model, Brandon Presley
Probation Officer Productivity: Using The Effort-Reward Imbalance Model, Brandon Presley
Electronic Theses and Dissertations
The purpose of this study is to determine the extent to which workplace efforts and rewards are associated with probation officer stress, overcommitment, health, and productivity. This research uses the effort-reward imbalance model, which is an indicator of job stress, on a group of criminal justice probation officers. The probation officers completed questionnaires regarding their perceptions of health, perceived reward, perceived effort, perceptions of overcommitment, and perceived productivity. Afterward, the responses were collected, and analyses were conducted using correlation and multiple regression to determine the extent to which perceptions of effort, reward, and overcommitment effect probation officer productivity and health. …
Data Representation In Machine Learning Methods With Its Application To Compilation Optimization And Epitope Prediction, Yevgeniy Sher
Data Representation In Machine Learning Methods With Its Application To Compilation Optimization And Epitope Prediction, Yevgeniy Sher
Electronic Theses and Dissertations
In this dissertation we explore the application of machine learning algorithms to compilation phase order optimization, and epitope prediction. The common thread running through these two disparate domains is the type of data being dealt with. In both problem domains we are dealing with categorical data, with its representation playing a significant role in the performance of classification algorithms. We first present a neuroevolutionary approach which orders optimization phases to generate compiled programs with performance superior to those compiled using LLVM's -O3 optimization level. Performance improvements calculated as the speed of the compiled program's execution ranged from 27% for the …
An Sos Conceptual Model, Lvc Simulation Framework, And A Prototypical Implementation Of Unmanned System Interventions For Nuclear Power Plant Disaster Preparedness, Response, And Mitigation, Matthew Davis
Electronic Theses and Dissertations
Nuclear power plant disasters can have severe and far-reaching consequences, thus emergency managers and first responders from utility owners to the DoD must be prepared to respond to and mitigate effects protecting the public and environment from further damage. Rapidly emerging unmanned systems promise significant improvement in response and mitigation of nuclear disasters. Models and simulations (M&S) may play a significant role in improving readiness and reducing risks through its use in planning, analysis, preparation training, and mitigation rehearsal for a wide spectrum of derivate scenarios. Legacy nuclear reactor M&S lack interoperability between themselves and avatar or agent-based simulations of …
Predicting Child Maltreatment Potential In Mothers Who Are Substance-Involved: A Study Of Childhood Adversity, Stress, Affectivity, Emotion Dysregulation, And Emotion Regulation Strategies As Mechanisms Of Action, Amanda Lowell
Electronic Theses and Dissertations
Compared to the general population, parents who are substance-involved are both more likely to have experienced adversity during childhood and to exhibit elevated child maltreatment potential later in life. Within this population, mothers with young children are particularly at-risk. In order to enhance scientific understanding of this phenomenon, this study identified and examined several characteristics that were shown previously to be related to substance misuse and to the experience and perpetration of maltreatment. These characteristics included stress, affectivity, emotion dysregulation, and emotion regulation strategies. The current study examined these variables collectively in order to clarify the mechanisms at play in …