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    On Steiner Symmetrizations of First Exit Time Distributions and Lévy Processes

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    The goal of this thesis is to establish generalized isoperimetric inequalities on first exit time distributions as well as expectations of Lévy processes.Firstly, we prove inequalities on first exit time distributions in the case that the Lévy process is an α-stable symmetric process At on R d , α P p0, 2s. Given At and a bounded domain D Ă Rd , we present a proof, based on the classical Brascamp-Lieb-Luttinger inequalities for multiple integrals, that the distribution of the first exit time of At from D increases under Steiner symmetrization. Further, it is shown that when a sequence of domains tDmu each contained in a ball B Ă R d and satisfying the ε-cone property converges to a domain D1 with respect to the Hausdorff metric, the sequence of distributions of first exit times for Brownian motion from Dm converges to the distribution of the exit time of Brownian motion from D1. The second set of results in this thesis extends the theorems from [5] by proving generalized isoperimetric inequalities on expectations of Lévy processes in the case of Steiner symmetrization.These results will then be used to establish inequalities involving distributions of first exit times of α-stable symmetric processes Atfrom triangles and quadrilaterals. The primary application of these inequalities is verifying a conjecture from Bañuelos in [3] for these planar domains. This extends a classical result of Pólya and Szegö in [28] to the fractional Laplacian with Dirichlet boundary conditions

    Investigation of the Gas-Phase Reactions of 2-Methoxypropene with Protonated Pyridine- and Aniline- Based Compounds

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    The purpose of this thesis research was to examine the gas-phase reactions of 2- methoxypropene (MOP) with protonated nitrogen-containing compounds, specifically pyridine, and aniline derivatives, in a linear quadrupole ion trap mass spectrometer. In addition, to maintain consistency with past experiments, several previously investigated sulfoxides were included in this study. The analytes were protonated via atmospheric pressure chemical ionization (APCI) in a linear quadrupole ion trap spectrometer, transferred into the ion trap, isolated, and then allowed to react with MOP inside the ion trap.All the protonated sulfoxides examined reacted with MOP to generate a stable adduct, as expected. They also transferred a proton to MOP. All protonated anilines reacted in the same manner with MOP. The diagnostic adduct formation reaction is proposed to involve proton transfer from the protonated analyte to MOP followed by addition of the neutral analyte to protonated MOP. In sharp contrast to sulfoxides and anilines, protonated pyridines were unreactive toward MOP. Therefore, the formation of a stable adduct is diagnostic for both sulfoxides and anilines but these compounds can be differentiated from pyridines due to the lack of reactivity of their protonated forms toward MOP

    Cardiovagal and Sympathetic Baroreflex Sensitivity and the Ability to Decenter

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    Previous studies have associated decentering, a non-judgmental view of emotions, with lower arterial stiffness and better nocturnal blood pressure dipping in adults. It is unknown however if autonomic regulation of blood pressure is linked to decentering. Therefore, the purpose of this study was to determine if decentering was related to cardiovagal or sympathetic baroreflex sensitivity (sBRS). Thirty-three adults (age 25±6 years; BMI 25±3 kg/m2 ) with resting blood pressure ≥120/80 mmHg volunteered for this study. All participants had a BMI \u3c30 kg/m2, and had no history of smoking, diabetes, or prescriptions for blood pressure or cardiac function. Participants completed an 11-item experiences questionnaire to evaluate decentering, and then were equipped for a supine autonomic evaluation. The autonomic evaluation included continuous recording of heart rate via 3-lead ECG, muscle sympathetic nerve activity (MSNA) via microneurography, and beat-to-beat blood pressure via finger photoplethysmography. Cardiovagal baroreflex sensitivity (n=33) included estimation of vagal activation by evaluating up-up relationships between systolic arterial pressure (SAP) and R-R intervals of the ECG. Vagal withdrawal was also estimated via the down-down relationships between SAP and R-R intervals. Spontaneous sBRS (n=17) was evaluated by assessing the relationship between changes in diastolic arterial pressure (DAP) in 3 mmHg bins vs. changes in MSNA burst incidence (bursts / 100 heart beats) in those with DAP-MSNA correlations \u3e0.70. Results from 2-tailed Pearson correlation analyses revealed that there was not a relationship between decentering and vagal activation (r=-0.07; p=0.71) or between decentering and vagal withdrawal (r=-0.28; p=0.12). There was a moderate, negative correlation between decentering and sBRS that lacked statistical significance (r= -0.35; p=0.17). Our findings suggest that there is not a clear link between decentering and autonomic regulation of blood pressure as estimated through cardiovagal baroreflex sensitivity, but the moderate correlation between decentering and sBRS should be explored in a larger sample size

    Utilization of Microrna Signatures as a Diagnostic Tool for Canine Urothelial Carcinoma

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    Background:UC is the most common urogenital cancer, comprising up to 2% of all naturally occurring neoplasia in dogs and can be challenging to diagnose. With early diagnosis, the disease can be controlled in most dogs with a good quality of life. MiRNAs are small noncoding RNAs that function by post-transcriptional regulation of gene expression. Their abundant presence and stability in the body make them promising tools for disease diagnosis.Hypothesis:A microRNA (miRNA) signature can be used to differentiate canine urothelial carcinoma (UC) from other lower urinary tract diseases.Literature review:There is an overlap of miRNA expression changes between normal physiologic processes, non-infectious and non-inflammatory conditions, infectious and/or inflammatory conditions, and neoplasia. Additionally, the mechanism of action of these overlapping miRNAs varies depending on the disease process. There is a lack of standardization of miRNA evaluation and consistency within a single evaluation method. Herein we evaluate three papers on miRNA expression in canine UC and compared the reported expression profile to human UC literature and identified experimentally validated targets of the dysregulated miRNA.Methods and results: (Aim 1) Using reverse transcriptase quantitative PCR (RT-qPCR), we assessed the effects of sample handling on miRNA expression in formalin-fixed Paraffinembedded (FFPE) tissue and urine sediment. We showed that the time of tissue fixation in formalin does not alter the detection of miRNA expression, but the inclusion of the muscularis layer altered the miRNA expression profile in bladder tissue. Additionally, miRNAs in urine sediment were proven to be stable despite the storage temperature for up to two weeks. (Aim 2) Using Next Generation Sequencing (NGS) with validation of findings via RT-qPCR, we evaluated differential miRNA expression in bladder tissue collected from normal canine urothelium and the invasive type of UC (iUC) to elucidate the dysregulated pathways. We found that twenty-eight miRNAs were differentially expressed (DE). The DE miRNAs were most often associated with gene silencing by miRNA, miRNAs in cancer, and miRNAs involved in DNA damage responses. Proteins involved include HRAS, KRAS, ARAF, RAF1, MAPK1, MAP2K1, MAPK3, FGFR3, EGFR, HBEGF, RASSF1, E2F2, E2F3, ERBB2, SRC, MMP1, and UP3KA. (Aim 3)Using RT-qPCR, expression of miR-214, miR-181a, miR-361, and miR-145 were evaluated. We failed to reject the null hypothesis that the relative gene expression in all groups was the same for any miRNA, nor did we find any multivariate summary that could effectively differentiate UC from inflammatory and non-neoplastic transitional cells.Conclusions:The findings within this thesis highlight the need for standardized methods for miRNA evaluation, support the use of stored samples for miRNA expression analysis, and show the importance of isolating the tissue of interest in FFPE. We defined the miRNome of iUC and investigated numerous protein pathways affected by dysregulation of differentially expressed miRNA in urothelial carcinoma. While we failed to reject our null hypothesis that the miRNA signature we evaluated could be utilized as a diagnostic tool for canine urothelial carcinoma, we showed the promise of miRNA as diagnostic tools and highlight several novel pathways that miRNA regulation affects in this disease

    Constraints on the Action of Positive Correspondences on Cohomology

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    Let X be a smooth projective variety of dimension n over an algebraically closed field K. We investigate constraints that the positivity of a correspondence (i.e., an algebraic n-cycle on X × X, usually considered modulo homological or numerical equivalence) imposes on its action on `-adic (or, over C, its singular) cohomology. For example, conjectures of DebarreJiang-Voisin imply nontrivial restrictions on this action whenever (in our terminology) a strictly pseudoeffective homological correspondence lies in the kernel of the pushforward by one of the projections X × X → X. We prove some new cases of these conjectures for correspondences on hyperelliptic varieties. In another direction, if the cycle class ∆X of the diagonal subvariety satisfies a certain positivity condition (which holds, for example, if X has nef tangent bundle), and A is a correspondence that is pseudoeffective (modulo numerical equivalence), then we show that the spectral radius of A (with respect to its action on cohomology) is attained on the even-degree cohomology. Under some further conditions (e.g. if K = Fq or X is an abelian variety), the spectral radius is in fact attained on the part of cohomology generated by iterates of A acting on powers of an ample divisor class. The key to these results is the existence and properties of a “good” cone C(X × X) of positive correspondences that is preserved under composition. If ∆X is an interior point of C(X ×X), then we show that X is fake projective (i.e. that X has the same `-adic betti numbers as Pn ). If C(X × X) is finitely-generated, then we show (under a few further conditions) that X is “fake rational homogeneous” in a certain sense (in particular, the cohomology of Xis entirely algebraic)

    Leveraging Multimodal Sensing for Enhancing the Security and Privacy of Mobile Systems

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    Mobile systems, such as smartphones, wearables (e.g., smartwatches, AR/VR headsets), and IoT devices, have come a long way from being just a method of communication to sophisticated sensing devices that monitor and control several aspects of our lives. These devices have enabled several useful applications in a wide range of domains ranging from healthcare and finance to energy and agriculture industries. While such advancement has enabled applications in several aspects of human life, it has also made these devices an interesting target for adversaries.In this dissertation, I specifically focus on how the various sensors on mobile devices can be exploited by adversaries to violate users’ privacy and present methods to use sensors to improve the security of these devices. My thesis posits that multi-modal sensing can be leveraged to enhance the security and privacy of mobile systems.In this, first, I describe my work demonstrating that human interaction with mobile devices and their accessories (e.g., stylus pencils) generates identifiable patterns in permissionless mobile sensors’ data, revealing sensitive information about users. Specifically, I developed S3 to show how embedded magnets in stylus pencils impact the mobile magnetometer sensor and can be exploited to infer a users incredibly private handwriting. Then, I designed LocIn to infer a users indoor semantic location from 3D spatial data collected by mixed reality devices through LiDAR and depth sensors. These works highlight new privacy issues due to advanced sensors on emerging commodity devices.Second, I present my work that characterizes the threats against smartphone authentication and IoT device pairing and proposes usable and secure methods to protect against these threats. I developed two systems, FaceRevelio and IoTCupid, to enable reliable and secure user and device authentication, respectively, to protect users’ private information (e.g., contacts, messages, credit card details) on commodity mobile and allow secure communication between IoT devices. These works enable usable authentication on diverse mobile and IoT devices and eliminate the dependency on sophisticated hardware for user-friendly authentication

    Ambient Ionization Mass Spectrometry for High Throughput Bioanalysis

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    The rapid analysis of complex samples using mass spectrometry (MS) provides valuable information in both point-of-care (e.g. drug testing) and laboratory-based applications, including the generation of spectral libraries for classification of biosamples, the identification of biomarkers through large-scale studies, as well as the synthesis and bioactivity assessments of large compound sets necessary for drug discovery. In all these cases, the inherent speed of MS is attractive, but rarely fully utilized due to the widespread use of sample purification techniques prior to analysis. Ambient ionization methodologies can help circumvent this drawback by facilitating highthroughput qualitative and quantitative analysis directly from the complex samples without any need for work-up. For instance, the use of swabs or paper substrates allows for rapid identification, quantification, and confirmation, of drugs of abuse from biofluids or surfaces of forensic interest in a matter of minutes, as described in the first two chapters of this dissertation. Faster analysis can be achieved using an automated desorption electrospray ionization (DESI) platform which allows for the rapid and direct screening of complex-sample microarrays with throughputs better than 1 sample per second, giving access to rich spectral information from tens of thousands of samples per day. The development of the bioanalytical capabilities of this platform, particularly within the context of drug discovery (e.g. bioactivity assays, biosample analysis), is described across most other chapters of this dissertation. The use of DESI, a contactless ambient ionization method developed in our laboratory and whose 20 years of history are overviewed in the introduction of this document, provides an additional advantage as the secondary microdroplets generated through the DESI process act as reaction vessels that can accelerate organic reactions by up to six orders of magnitude, facilitating on-the-fly synthesis of new compounds from arrays of starting materials. Unique implications of this microdroplet chemistry in the prebiotic synthesis of peptides and spontaneous redox chemistry at air-solution interfaces, together with its practical applications to the synthesis of new drug molecules, are also overviewed. The success obtained with the first automated DESI-MS system, developed within the DARPA Make Itprogram, led to increased interest in a new-generation platform which was designed over the past year, as overviewed in the last section of this dissertation, and which is currently being installed for validation prior to the transfer of the technology to NCATS, where we anticipate it will make a significant impact through the consolidation and acceleration of the early drug discovery workflow

    Enhancing Construction Workers Safety: The Design and Implementation of Interactive-Motivational Noise-Cancelling Headphones

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    Noise-induced hearing loss (NIHL) is a significant occupational health concern in the construction industry, necessitating effective hearing protection for workers. This project explores the detrimental consequences of environmental pollutants, specifically noise pollution common in construction settings. The research incorporates user interviews with construction workers and managers to identify challenges and motivations surrounding the use of hearing protection devices.My findings underscore the necessity of addressing pollution in the construction industry to safeguard the well-being of workers. Noise pollution emerges as a primary concern, leading to hearing loss, stress, decreased productivity, and safety hazards. The research revealed that workers grapple with obstacles, including discomfort, lack of awareness, and cost barriers, while also recognizing driving forces, including fear of hearing loss and the encouragement of supervisors. The design process involved thorough research, including a literature review, competitive analysis, and semi-structured user interviews, resulting in an advanced hearing protection device that prioritizes effective communication, cleanliness, and user comfort. The final product incorporates innovative features such as lighting indicators, a compact charging case, strategically positioned buttons, secure fit with magnets, and a range of color options. Furthermore, the accompanying application features customizable ambient sounds, performance feedback, and gamification elements

    User Experience Study of Screen Readers for Visually Challenged Users

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    The study investigates the user experience of visually impaired people using screen readers, concentrating on their accessibility and usability when navigating digital content. Screen readers are indispensable instruments for the blind and visually impaired, facilitating the completion of online tasks and access to information. While screen readers offer benefits such as customization and accessibility, they also present users with challenges such as cognitive burden, sequential navigation, and limitations with multimedia content.The research takes a user-centric approach, taking into account the particular requirements and preferences of visually impaired users. By conducting empirical research, the study gains valuable insights into the experiences, requirements, and pain points of screen reader users. The objective is to identify areas for enhancement and create solutions that enhance the user\u27s efficiency and satisfaction.Recognizing the diverse subcategories within the visually impaired population, the thesis argues for design approaches that are tailored to specific needs. In addition, the incorporation of existing artificial intelligence systems, such as image caption generation and text extraction, is investigated to improve the functionality and usability of screen readers.Through this research, the thesis emphasizes the significance of creating digital content that is both functional and accessible. By embracing the curb cut effect and incorporating empirical research findings, developers can cultivate a more inclusive and equitable online environment for all users, thereby promoting inclusivity and ensuring that visually impaired users can effectively interact with digital content

    The Complexities of Green Infrastructure

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    The Wabash River is the most extensive river system in Indiana. The river drains two-thirds of Indiana’s 92 counties, which can have issues associated with stormwater runoff (Weist, 1981). As precipitation runs off impervious surfaces, it can carry high concentrations of pollutants, such as excess nitrogen and phosphorus, pet waste, and automobile fuel. Prior to impervious runoff entering the river, preexisting contaminants include industrial waste (acid mine drainage and oil field brines), municipal waste, and sediment (Weist, 1981). Thus, stormwater runoff can negatively impact the Wabash River watershed. On top of this pollution, Lafayette and West Lafayette have combined sewer overflows (CSOs). A CSO collects wastewater and stormwater in a single sewer system, with a majority of collected waste transported to the wastewater treatment plant. During significant rainfall events, the sewer system overflows with a mixture of raw wastewater and precipitation, spilling into the Wabash River. The impact of a CSO system can be physical, chemical, microbiological, or combined (Marsalek, 2003). Erosion and sediment transport, temperature rise, dissolved oxygen depletion, eutrophication, and acute or chronic toxicity are some of the ecological impacts of urban CSO systems. Additionally, in a survey conducted by Purdue University in 2016, Greater Lafayette urban residents acknowledged the Wabash River as contaminated and unusable (Gao et al., 2016). The community members indicated that they would enjoy the river if it were clean and managed adequately. Future protection of the Wabash River is necessary to prevent runoff from entering the watershed and developing these harmful environmental effects. I was interested in partaking in Dr. Lindsey Payne’s course “Urban Water Projects” (EEE 495) to involve myself in community projects in Greater Lafayette. The course is offered to students with an interest in community-engaged design processes of green infrastructure. The purpose of installing green infrastructure, alternatively best management practices (BMPs), is to mitigate the effects of stormwater runoff entering the Wabash River. Civic engagement, design, addressing local water sustainability issues, and education are some of the key concepts required when students integrate and promote green infrastructure solutions in the community. The purpose of including this course in my undergraduate career was to educate myself and the community about ecological engagement opportunities

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