Doctor of Philosophy, The Ohio State University, 2020, Electrical and Computer Engineering

The new generation of wireless networks is expected to be a key enabler of a myriad of new industries and applications. Disruptive technologies such as autonomous driving, cloud gaming, smart healthcare, and virtual reality are expected to rely on a robust wireless infrastructure to support those applications' vast and diverse communication requirements. The successful realization of a large number of those applications hinges on timely information exchange, and thus, Latency arises as the critical requirement essential to unlock the true potential of the new 5G wireless generation. In order to ensure reliable low latency communication, new network algorithms and protocols prioritizing latency need to be developed across different layers of the network stack. Furthermore, a theoretical framework is needed to better understand the behavior of delay at the wireless edge and the proposed solutions' performance. In this dissertation, we study the problem of designing algorithms for low latency communication by addressing traditional problems such as resource allocation and scheduling from a delay-oriented standpoint, as well as, new problems that arise from the new 5G architecture such as caching and Heterogeneous Networks (HetNets) access. We start by a addressing the problem of designing real-time cellular downlink resource allocation algorithms for flows with hard deadlines. Attempting to solve this problem brings about the following two key challenges: (i) The flow arrival and the wireless channel state information are not known to the Base Station (BS) apriori, thus, the allocation decisions need to be made in an online manner. (ii) Resource allocation algorithms that attempt to maximize a reward in the wireless setting will likely be unfair, causing unacceptable service for some users. We model the problem of allocating resources to deadline-sensitive traffic as an online convex optimization problem. We address the question of whether we can efficiently solve t (open full item for complete abstract)

Committee: Eylem Ekici (Advisor); Ness Shroff (Advisor); Atilla Eryilmaz (Committee Member) Subjects: Electrical Engineering

PhD, University of Cincinnati, 2011, Allied Health Sciences: Communication Sciences and Disorders

Background: Previous human auditory brainstem response (ABR) studies have suggested that the right ear auditory network preferentially processes a spectrotemporally complex speech syllable and the left ear auditory network preferentially processes temporally devoid spectral stimuli. Human cortical studies also suggest lateralization effects to spectral versus temporal stimuli. However, it remains unclear if the reported brainstem lateralization effects may be due to the spectrotemporal content or the higher order lexical content of the evoking speech stimulus. Also, the lateralization effects observed at the cortical level in late evoked auditory potentials are based upon responses obtained well after the stimulus has arrived to the auditory cortices (~100 ms). Lateralization effects to spectrotemporally complex stimuli are unknown upon first arrival to the auditory cortices or in the auditory middle latency Pa response which occurs approximately 30 ms post-stimulus. Purpose: The purpose of this study was to gain a better understanding of how the human auditory processing system encodes spectrotemporally complex acoustic stimuli from subcortical levels to first arrival at the bilateral cortices. Research Design: This study is a comparative analysis of both brainstem frequency following responses (FFRs) and cortical auditory middle latency responses (AMLRs) to spectrotemporally complex speech and spectrally complex nonspeech stimuli evoked from right and left ear stimulation in normal hearing adult females. Study Sample: ABR and AMLR responses elicited by a spectrotemporally complex speech stimulus /da/ and a spectrally complex nonspeech stimulus were obtained in a group of twenty right-handed normal hearing adult females. Data Collection and Analysis: Electrophysiological brainstem FFRs and AMLRs were recorded using a 40 ms synthesized speech syllable /da/ presented both forwards and backwards in addition to a 40 ms complex tone. Monaural ipsilateral FFRs and A (open full item for complete abstract)

Committee: Fawen Zhang PhD (Committee Chair); James Eliassen PhD (Committee Member); Robert Keith PhD (Committee Member); Peter Scheifele PhD (Committee Member) Subjects: Audiology

Doctor of Philosophy, Case Western Reserve University, 2022, Molecular Virology

HIV proviruses enter latency when effector cells transition to a memory T-cell phenotype. We have recently discovered major rearrangements in the nuclear landscape during effector cell transition to quiescence. To visualize proviral localization in the nucleus, we developed a novel and highly sensitive immuno-CasFISH technique in which we tagged HIV DNA using multiple RNA-guided endonuclease-deficient Cas9-mediated complexes directed to the 5' LTR of the HIV-1 genome which are detected by antibody staining. Using immuno-CasFISH we monitored the spatiotemporal dynamics of the HIV DNA from acute infection, through effector cell transition to quiescence when the proviruses were latent and subsequently after reactivation. In Th17 cells acutely infected with a single-round HIV-1 reporter virus, HIV DNA was found at the nuclear envelope together with cleavage and polyadenylation specificity factor 6 (CPSF6), as early as 24 hours post-infection. Following nuclear entry, HIV DNA/CPSF6 complexes were detected at high frequency in the nuclear periphery and intermediate zones. However, cell transition to quiescence which established viral latency led to a high frequency of perinucleolar localization of HIV DNA with significant loss of CPSF6 over time. Similarly, the majority of latent proviruses seen in memory T-cells from well suppressed patients accumulate in the perinuclear region. Reactivation of the latently infected cells (QUECEL Th17) through their T-cell receptors caused the rapid accumulation of 7SK snRNA, Tat and P-TEFb with the proviral DNA. In confirmation of these results, in situ hybridization showed that nascent viral HIV RNA transcripts were detected emanating from the proviral transcriptional site localized in the perinucleolar zones, in both Th17 cells and patient-derived memory CD4+ T cells. Interestingly, in the rare cells carrying two proviruses located at different distances from the nucleolus, proviruses nearest the nucleolus accumulated far more (open full item for complete abstract)

Committee: Jonathan Karn (Advisor); Henry Boom (Committee Member); Saba Valadkhan (Committee Member); Jacek Skowronski (Committee Chair) Subjects: Microbiology; Molecular Biology; Virology

Doctor of Philosophy, The Ohio State University, 2021, Computer Science and Engineering

Performance analysis is fundamental and significant to software development in both academia and industry. Especially in the era of post Moore's law, performance analysis becomes increasingly important and challenging due to stagnant per-core CPU performance and slow increase of core count. In addition, the large scale of trace data generated by applications, operating systems and hardware (like performance monitor counter) make performance analysis more difficult. To solve these challenges, we need to design performance analysis methods systematically and holistically leveraging the information from applications, operating systems, and hardware. In this dissertation, I focus on identifying and understanding performance problems related to two key performance metrics: throughput and latency. First, we propose wPerf, a generic off-CPU analysis method to identify waiting events that limit the maximal throughput of a multi-threaded application. To achieve this, we not only need to understand an event's impact on threads waiting for this event (i.e., local impact), but also need to understand whether its impact can reach other threads that are involved in request processing (i.e., global impact). To address these challenges, wPerf computes the local impact of a waiting event with a technique called cascaded re-distribution; more importantly, wPerf builds a wait-for graph to compute whether such impact can indirectly reach other threads. By combining these two techniques, wPerf essentially identifies events with large impacts on all threads. We apply wPerf to a number of open-source multithreaded applications. By following the guide of wPerf, we are able to improve their throughput by up to 4.83×. Second, we present our experience to understand latency variance caused by kernel and hardware events, which are often invisible at the application level. For this purpose, we have built VarMRI, a tool chain to monitor and analyze those events in the long term. The design (open full item for complete abstract)

Committee: Yang Wang (Advisor); Jason Flinn (Committee Member); Feng Qin (Committee Member); Xiaodong Zhang (Committee Member) Subjects: Computer Science

Master of Science, The Ohio State University, 2020, Electrical and Computer Engineering

Power is an important issue for a data center as the workloads grow rapidly, especially as machine learning services increase exponentially, and it is essential to control the performance of systems to save energy cost. For customers, inference latency of machine learning services is their key concern, but accelerating inference means to increase performance level of servers. Also, downgrading power consumption of a system leads to bad service. Namely, it is important to balance the interaction between power consumption and service level agreement simultaneously. This thesis proposes a system to control the power and inference latency of machine learning workloads, which are evaluated by MIMO control approach and proportional feedback control method. We also apply theoretical methodology to systematically design the control loop with assurance of stability and performance such as settling time and inference accuracy. Our results show that MIMO control gives better performance in terms of settling time and steady-state errors, and the error rate is less than 2% for latency control and less than 1% for power control, which are precise enough for most applications.

Committee: Xiaorui Wang (Advisor); Wladimiro Villarroel (Committee Member) Subjects: Computer Engineering; Electrical Engineering

PhD, University of Cincinnati, 2020, Medicine: Molecular Genetics, Biochemistry, and Microbiology

Growth differentiation factor 8 (GDF8), a.k.a. myostatin, is a member of the activin subclass within the larger TGFß superfamily of signaling ligands that contains over 30 distinct members. Discovered in 1997, GDF8 quickly became characterized as a negative regulator of muscle mass because a highly active GDF8 caused muscle wasting or atrophy. In contrast, when GDF8 is rendered inactive through extracellular inhibitors or mutations, massive muscle gain was observed. This discovery generated massive interest within the pharmaceutical industry to manufacture inhibitors for GDF8 to combat a variety of muscle wasting diseases. A better understanding of how GDF8 is regulated in vivo is imperative to develop efficacious and novel inhibitors against GDF8. The activity of GDF8 is tightly regulated in vivo by several different processes. TGFß ligands are synthesized as large precursor proteins with a N-terminal signal sequence and prodomain followed by the mature signaling domain. The prodomain is cleaved from the mature domain, but unlike most other TGFß family members, GDF8 forms a high affinity interaction with its prodomain rendering it inactive or latent. Prior to our work, the molecular mechanisms dictating latency were not well understood but were hypothesized to be like the latent TGFß1 procomplex. Using the TGFß1 procomplex as a model, we identified residues critical for a stable latent GDF8 procomplex. Furthermore, the structure of the latent GDF8 procomplex was solved by another laboratory and our mutants could be further characterized to determine the molecular mechanisms of GDF8 latency. In order to signal, latent GDF8 needs to be activated by a member of the tolloid family of metalloproteases which proteolytically cleaves the prodomain. While the site of tolloid cleavage on the GDF8 prodomain has been identified, how tolloid recognized the prodomain as a substrate was unknown. Unlike other proteases, tolloid has no concrete consensus sequence required for cleav (open full item for complete abstract)

Committee: Thomas Thompson Ph.D. (Committee Chair); Sean Davidson Ph.D. (Committee Member); Rhett Kovall Ph.D. (Committee Member); Jeffery Molkentin Ph.D. (Committee Member); David Wieczorek Ph.D. (Committee Member) Subjects: Molecular Biology

Master of Arts, The Ohio State University, 2020, Communication

Our ability to test and falsify theories rests on valid and reliable measurement. Minimizing noise, or measurement error, is a hurdle that researchers must overcome. Researchers use state-of-the-art tools to investigate the cognitive underpinnings of human communicative behavior and measurement error is likely to differ by instrument. It is important to determine if a given instrument is sufficiently accurate to extract signal from noise. Reaction time is commonly used to measure cognitive processes during media use. A reaction time measurement tool has been recently implemented in Asteroid Impact, an open source, naturalistic, experimental video game stimulus. We tested if reaction time latency differed across computer operating system (macOS, Windows 10, Ubuntu 18.04), software (Python 2, Python 3), and trial modality (audio, visual) in Asteroid Impact. We used an Arduino microcontroller to generate a ground truth value of average response time latency. Specifically, we measured the latency between the onset of visual and auditory trials and a response from the Arduino. The Arduino was programmed to look for changes in luminance (visual trial) or sound amplitude (audio trial) every millisecond. When a change was detected, the Arduino was programmed to issue a keypress response. Any observed latency between trial onset and the microcontroller's response reflects measurement error in the computer hardware and software. Ideally, this latency will have a small mean and variance, which would indicate that Asteroid Impact is accurate in measuring reaction times. All code to fully reproduce and replicate this study is available on GitHub (https://anonymous.4open.science/r/8b618f1e-6cf4-4bdd-9e3b-4058a37bfb53/). ANOVA results showed a significant three-way interaction F (2, 1188) = 199.95, p < .001, η2 = .25. Auditory trials using Python 3 on macOS had the lowest latency (M = 44.6, SD = 8.4). Auditory trials using Python 2 on Ubuntu 18.04 had the longest latency (M (open full item for complete abstract)

Committee: Gerald Kosicki Ph.D. (Advisor); Richard Huskey Ph.D. (Committee Member) Subjects: Communication

MS, Kent State University, 2019, College of Education, Health and Human Services / School of Health Sciences

Because obesity and sleep are very complex multifactorial, there is a need to look at the variety of variables like BMI, sleep quality, duration, patterns and cultural impact. This study purpose was compared the differences in sleep duration based on total hours of sleep, quality based on PSQI, and sleep patterns based on weekdays/weekends bedtime shift and sleep hours shift; between 994 undergrad and postgrad students of varying BMI statuses (underweight, normal weight, overweight, and obese) from both universities KSU and KAU. Students who had any of this condition bariatric surgery, eating disorders, Prader-Willi/ Bardet-Biedl syndromes, underactive thyroid (hypothyroidism), pregnancy, less than 18 years old, sleep less than three hours per night, or/and have BMI less than 18 or more than 33 were excluded. A 2x2x4 factorial ANOVA used to analysis sleep quality, duration and patterns; and chi square used to analysis PSQI components. This study found that short sleep duration (P=0.044), and sleep efficiency (P=0.044) were linked to obesity. Moreover, KAU students had shorter sleep duration (P=0.001) with less quality (P=0.001) and higher bedtime shift (P=0.000) than KSU students. Moreover, stress, anxiety, depression, insomnia, and overthinking were the most common sleep troubles at college students. These findings suggest the need for educating college students about sleep in general (number of hours they need, improve sleep quality, and other related advices); besides, learning how to control theses influences (stress, anxiety, insomnia, depression, and overthinking) to enhance their sleep and their overall well-being and avoid future related health issues.

Committee: Natalie Caine-Bish (Advisor); Karen Gordon (Committee Member); Jamie Matthews (Committee Member) Subjects: Gender; Nutrition; Public Health; Public Health Education

Doctor of Philosophy (PhD), Ohio University, 2019, Experimental Psychology (Arts and Sciences)

Background: Smoking is the number one preventable cause of death. To improve cessation rates, a better understanding of relapse antecedents is needed. Initial research indicates stress during quit attempts increases cravings and decreases smoking latencies, but these studies are limited in number and by the stressors used (i.e., primarily negative imagery). Similarly, initial research indicates trait rumination is positively associated with smoking relapse. However, no study has assessed the effects of state rumination on smoking relapse. So, the present study assessed the effects of a socially-evaluative stressor and state rumination on indicators of relapse (e.g., craving, smoking latency, ad-libitum smoking) among nicotine-deprived smokers. Methods: Following a nicotine-satiated baseline, 28 daily smokers underwent nicotine deprivation (M = 14.05, SD = 1.38 hrs). Afterwards, participants completed an acute psychosocial stressor. Next, participants were randomized to either Ruminate (n = 12) or to be Distracted (n = 16) before completing a laboratory smoking latency task. Craving was assessed after each task. Lastly, participants completed a 24-hour follow-up survey about latency to smoke and number of cigarettes smoked. Results: Stress significantly increased craving. However, the Rumination and Distraction groups did not differ in cravings, smoking latencies, or ad-libitum smoking. Conclusions: These findings replicate a small number of prior studies' findings that socially-evaluative stressors increase nicotine-deprived smokers' cravings. However, there was no effect of Rumination relative to Distraction on indicators of relapse. These findings are informative about the effects of adverse states on smoking relapse.

Committee: Peggy Zoccola PhD (Advisor) Subjects: Behavioral Psychology; Behavioral Sciences; Experimental Psychology; Psychology

Master of Sciences, Case Western Reserve University, 2018, EECS - Electrical Engineering

Computer use in high dependability applications is rapidly increasing. However, even when correctly designed, computer systems can still suffer from temporary errors due to various factors. So to increase the reliability of modern computer systems, they should be able to detect, locate, isolate and recover from software, hardware or security attacks errors. Fault injection simulates the effect of unexpected errors on the system; they are useful in the evaluation and validation of dependable systems. As part of this thesis, we developed an efficient transient fault injection and detection system (ETFIDS) for evaluating the fault tolerance and fault response of software applications. Despite being portable and of high performance, ETFIDS introduced a new fault outcome analysis technique which evaluates, concurrently, both the faulty and the fault-free system behavior during runtime for better analysis and efficiency.

Committee: Daniel Saab (Advisor); Christos Papachristou (Committee Member); Francis Merat (Committee Member) Subjects: Electrical Engineering

Doctor of Philosophy, Case Western Reserve University, 2018, Pathology

Breast cancer is the most common malignancy and second most common cause of cancer-related death in women, a clinical challenge exasperated by the lack of targeted therapies for metastasis, the most deadly component of breast cancer. Although the molecular mechanisms underpinning the dissemination of primary breast cancer cells to distant tissues remain incompletely understood, long noncoding RNAs (lncRNAs) have emerged as potent regulators of breast cancer development and progression, including the metastatic spread of disease. Through in silico and biological analyses, we identified a novel lncRNA, BMP/OP-Responsive Gene (BORG), whose expression directly correlates with aggressive breast cancer phenotypes, as well as with metastatic competence and disease recurrence in multiple clinical breast cancer patient cohorts. Mechanistically, BORG elicits the metastatic outgrowth of latent breast cancer cells by promoting the localization and transcriptional repressive activity of TRIM28, which binds BORG and induces substantial alterations in carcinoma proliferation and survival. Moreover, inhibiting BORG expression in metastatic breast cancer cells impedes their metastatic colonization of the lungs of mice, implying that BORG acts as a novel driver of the genetic and epigenetic alterations that underlie the acquisition of metastatic and recurrent phenotypes by breast cancer cells. Interestingly, the BORG-dependent transcriptome demonstrates enhanced signaling through survival and viability pathways, as well as decreased activation of cell death pathways. Accordingly, we determined that BORG expression is broadly promoted by environmental and chemotherapeutic stresses, a transcriptional response that facilitates the survival of breast cancer cells. These effects rely upon a BORG-induced induction of NF- B signaling as part of a feed-forward NF- B signaling loop, as well as its ability to bind and activate RPA1. Taken together, our mechanistic insights into BORG-m (open full item for complete abstract)

Committee: William Schiemann (Advisor); Hannah Gilmore (Committee Chair); Saba Valadkhan (Committee Member); Mark Jackson (Committee Member); Goutham Narla (Committee Member) Subjects: Oncology; Pathology

Doctor of Philosophy, Case Western Reserve University, 2017, Molecular Biology and Microbiology

HIV-1 infection remains a challenging infectious disease. Although highly active antiretroviral therapy (HAART) is effective in suppressing viral replication below detectable levels, it fails to eradicate HIV-1. Interruption of HAART results in reactivation of HIV-1 replication from latent proviruses which mainly reside in CD4+ resting memory T cells. Latent HIV-1 is very stable in the body even under HAART and considered the last barrier for HIV-1 cure. Current efforts seek to understand mechanisms underlying the formation of latent HIV-1 reservoirs and develop drugs capable of reactivating latent proviruses. We demonstrate a critical role for the Polycomb repressive complex 2 (PRC2), the histone H3 lysine 27 methyltransferase complex, for the maintenance of HIV-1 latency in Jurkat T cells. Both depletion and knockout of EZH2, a catalytic subunit of PRC2, spontaneously induce latent proviruses and strongly sensitize them for exogenous stimuli. However, knockout of G9a, a histone H3 lysine 9 methyltransferase, fails to reactivate latent HIV-1 in this system. By contrast, depletion of EZH2 and G9a in Jurkat T cells prior to HIV-1 infection significantly reduce levels of the resulting silenced viruses. In contrast to the Jurkat T cells, inhibition of EZH2 (by GSK-343 or EPZ-6438) and G9a (by UNC-0638) in resting memory T cells cultured ex vivo or isolated from infected patients receiving HAART caused moderate reactivation of latent proviruses. We conclude that both PRC2 and G9a are required for the establishment and maintenance of HIV-1 latency in T cells. EZH2 inhibitors (GSK-343 and EPZ-6438), or the G9a inhibitor UNC-0638 are potential candidates for use as latency-reversing agents in clinical studies. In addition, the role of H3K27 demethylase UTX1 as an inhibitor of HIV-1 latency in T cells is also characterized. Compared to latent proviruses, UTX1 is more enriched at the promoter of reactivated HIV-1. Its depletion restricts the reactivation of latent HIV-1 in (open full item for complete abstract)

Committee: Jonathan Karn PhD (Advisor); Jacek Skowronski PhD (Committee Chair); Paul Macdonald PhD (Committee Member); David McDonald PhD (Committee Member) Subjects: Molecular Biology; Virology

Doctor of Psychology (Psy.D.), Xavier University, 2016, Psychology

Previous eye tracking research suggested that children and adolescents with Autistic Disorder (AD) exhibit atypical gaze patterns while observing dynamic social interactions. The relationship among atypical gaze patterns, social ability, and underlying biological conditions has yet to be investigated. The present study utilized eye tracking technology to investigate the gaze patterns of 26 typically developing children and adolescents, ages 5-17, and 38 aged-matched peers with AD as they viewed a dynamic play scene. Between-group differences in the static activation level of the extracellular signal-regulated kinase (ERK) pathway in peripheral lymphocytes were also explored. Children and adolescents with AD displayed shorter fixations on faces and took longer to fixate on a face compared to participants without AD. Additionally, participants with AD had almost twice the amount of static ERK activation in peripheral lymphocytes than control participants. The atypical gaze patterns of participants with AD were not associated with social ability or ERK activation level. The findings demonstrate that atypical gaze extends to social play scenes for individuals with AD. Further investigation is needed on the implications of the ERK pathway in children and adolescents with AD and the extent to which eye tracking research directly relates to real-world social abilities.

Committee: Janet Schultz Ph.D. (Committee Chair); Kathleen Hart Ph.D. (Committee Member); Craig Erickson Ph.D. (Committee Member) Subjects: Behavioral Psychology; Cellular Biology; Developmental Psychology

MS, University of Cincinnati, 2016, Medicine: Immunology

Herpes Simplex Viruses 1 and 2 (HSV-1 and -2) are ubiquitous, contagious human pathogens, with estimated 776,000 new infections in the USA yearly. Majority of primary infections occur in early childhood during delivery or through transmission by parent/guardian and it is estimated that 90% of the world population is seropositive for HSV-1 by the age of 65. Primary infection presents as cold sores and is self-contained in immune-competent host. HSV-1 has ability to evade immune clearance and reside undetected in the host by establishing latency in the trigeminal ganglia. Recurrent, sporadic episodes of viral reactivation are mostly mild, but in immune-compromised individuals may cause encephalitis and keratitis. Untreated viral encephalitis has a 70% mortality rate. Early intervention with antiretroviral therapy improves the outcome, but leaves over 60% of patients with lifelong neurological morbidities. Keratitis, induced by HSV-1, is the leading cause of virally induced blindness. This review summarizes viral structure, mode of infection, and clinical presentation, as well as the role of immune system and gene remodeling in the pathogenesis of HSV-1.

Committee: Jonathan Katz Ph.D. (Committee Chair); Nicolas Nassar Ph.D. (Committee Member); Jose Cancelas-Perez M.D. (Committee Member); Andrew Herr Ph.D. (Committee Member) Subjects: Biology

PhD, University of Cincinnati, 2015, Allied Health Sciences: Communication Sciences and Disorders

Special Operations in Command Multi-Purpose Canines (SOCOM MPCs) are extremely effective at executing tasks necessary for the protection, security and welfare of the human population, often in the most demanding environments. They receive extensive training which is vital to ensure the successful outcome of each mission as required by special operations. Therefore, Multi-Purpose Canines play an important role in preventing injury and death to United States military and service personnel. However, there are physical and psychological consequences than can result from the execution of required tasks. These consequences can substantially reduce their ability to perform effectively in theatre. During training and wartime, SOCOM MPCs are exposed to significant noise levels on a regular basis, without the current use of hearing protection. Evidence suggests these dogs are presenting with audiologic abnormalities, including auditory deprivation, hyperacusis and deficits in auditory processing. Audiologic symptoms can be detectable and measurable by objective criteria, namely the Brainstem Auditory Evoked Response (BAER). The BAER test is a means of obtaining ear specific information from recording neural activity generated from the cochlear nerve and brainstem in response to a controlled sound stimulus. Since the 1970s, BAER testing has been used as the gold standard for assessing auditory function in canines (Scheifele & Clark, 2012). The use of BAER testing in SOCOM MPCs to assess auditory function and threshold is investigated. Results from SOCOM MPCs are compared to findings from Non-MPCs, with no known significant exposure to noise. Ranges were established for important waveform components of the BAER test across several intensities. Additionally, the preliminary use of the Auditory Middle Latency Response (AMLR) is investigated in Non-MPCs. The AMLR is a means of assessing higher order auditory-cognitive function. Findings are encouraging for both audi (open full item for complete abstract)

Committee: Peter Scheifele Ph.D. (Committee Chair); Brian Earl Ph.D. (Committee Member); Sarah Couch Ph.D. (Committee Member); Robert Keith Ph.D. (Committee Member) Subjects: Audiology

Master of Sciences, Case Western Reserve University, 2015, Molecular Virology

The eradication of HIV-infected cells is complicated by the virus's ability to integrate within the host cell genome without subsequent expression. Although the administration of HAART can reduce viremia to levels below limits-of-detection, expression of latent provirus can be reactivated, leading to the production of new virus particles resulting in the infection of new cells. We have identified several nuclear receptors as potential candidates for maintaining proviral latency in either CD4+ T-cells or microglial cells. We will generate CRISPRs targeting diverse nuclear receptors to produce complete gene knockouts and perform subsequent experiments to understand their role in latency. Ultimately using this the CRISPR/Cas9 system, we will develop a more complete understanding of the molecular interactions leading to proviral latency.

Committee: Jonathan Karn (Advisor); John Tilton (Committee Chair); Gary Landreth (Committee Member); Cornelia Bergmann (Committee Member) Subjects: Molecular Biology; Virology

Master of Science (M.S.), University of Dayton, 2014, Electrical Engineering

This paper investigates the use of fiber optic comminucation media in a digital flight control system. A number of recommendations are included to allow reliable use of fiber optics in this application. A proposed fiber optic media, AFDX, is studied using dynamic, real time models. The effect of latency introduced by AFDX is studied for an F-16 aircraft model. Finally, the effect of latency and jitter are correlated using a simpler induction heater model and PID controller.

Committee: John Weber Ph.D. (Committee Chair); Raul Ordonez Ph.D. (Committee Member); Donald Kessler Ph.D. (Committee Member) Subjects: Aerospace Engineering; Electrical Engineering; Engineering

Doctor of Philosophy, University of Toledo, 2014, Higher Education

The higher education marketplace in the United States has changed. Competition has increased, and modes of instructional delivery have changed to meet demand, yet enrollment at post-secondary institutions in the United States has been declining. Students have not persisted through the pre-matriculation funneling stages of the enrollment process with the same consistency as they have in the past. The purposes of this dissertation were (a) to assess the period of latency between application and enrollment and (b) to determine whether students would be more likely to persist through the recruitment funnel if institutions altered their enrollment calendars. The researcher reviewed data from a single-proprietary institution comprised of multiple campuses located throughout the eastern and southern portions of the United States to determine the influence of latency, within the recruitment funnel, upon yield. Upon the exploration of nearly 4 years worth of data and more than 32,000 student files, the researcher was able to determine that increasing the number of start dates did not practically influence students'/consumers' purchasing behavior at Career College. Furthermore, shortening the latency period did little to nothing to impact the percentage of students persisting through the recruitment funnel. However, the findings did reveal significant behavioral differences between traditional and non-traditional students. In summation, the findings revealed that students are essentially consumers who will act upon their desire to purchase products (e.g., a college degree) in a time frame consistent with their own immediate needs and opportunity costs, regardless of institutional efforts to influence them to do otherwise. In other words, latency is an institutionally controllable factor that does not appear to alter the course of enrollment yield among traditional students.

Committee: Penny Poplin Gosetti Ph.D. (Committee Chair); Ronald Opp Ph.D. (Committee Member); William Getter D.P.A. (Committee Member); David Black Ph.D. (Committee Member) Subjects: Economics; Higher Education; Higher Education Administration

Doctor of Philosophy, The Ohio State University, 2014, Microbiology

By the end of 2011, there were approximately 34 million HIV-infected individuals and more than 25 million AIDS-related deaths worldwide. The lack of successful prevention strategies and economic constraints of antiretroviral regimens highlight the importance of HIV-1 research. Current research goals aim to understand molecular mechanisms of transmission and infection so preventative measures and superior treatment regimens can be devised. This dissertation has two major foci: determining how viral genetic diversity contributes to transcriptional regulation within in utero mother-to-child transmission and understanding how pharmacological modulation of epigenetic pathways regulates HIV latency. Without intervention, mother-to-child transmission accounts for approximately 30% of all HIV infections; however, MTCT is responsible for 90% of pediatric HIV infections. Approximately 20% of all HIV-1 mother-to-child transmission (MTCT) occurs in utero (IU), with little understanding of the molecular mechanism underlying this event. During IU MTCT, viral variants must traverse an intact placental barrier to reach fetal circulation, creating a genetic bottleneck. As a model of transmission, we hypothesize that viral genetic diversity within the U3R is associated with selection for gestational transmission. To this end, we used single template amplification to isolate 517 U3R sequences from maternal, placental, and infant plasma derived from seventeen HIV-infected Malawian women. Specific TF sequence polymorphisms were not significantly associated with IU MTCT; thus, we were unable to detect a promoter genotype associated with gestational transmission. We then tested the hypothesis that genetic variability of the HIV-1 U3R associates with a transcriptional phenotype. To test this hypothesis, we cloned 90 U3R sequences and assayed promoter activity in multiple cell lines. Although we observed significant, yet highly variable promoter activity, there was no association between me (open full item for complete abstract)

Committee: Jesse Kwiek PhD (Advisor); Chad Rappleye PhD (Committee Member); Li Wu PhD (Committee Member); Marshall Williams PhD (Committee Member) Subjects: Microbiology; Molecular Biology; Virology

Master of Science (MS), Wright State University, 2013, Microbiology and Immunology

Herpes simplex type 1 (HSV-1) quiescent infection was established in L929 cells, murine fibroblasts, and in Neuro-2A (N2A) cells, mouse neuroblastoma, by treating them with the nucleoside analogue acyclovir (ACV) 24 hours before infection. Subsequent release of virus from the non-productive state was accomplished by treating the cells with the histone deacetylase inhibitor trichostatin A (TSA). Treatment of both L929 and N2A cell lines with ACV 24 hours before infection induced protection from HSV-1 cytopathic effect. A quiescent state was confirmed by absence of virus plaques when supernatant fluids from ACV-treated HSV-1 infected cultures were titered on Vero cell monolayers. Acyclovir was maintained in the cell culture medium for one day before infection and two days post infection. Removal of ACV from the culture medium did not permit reactivation of virus as determined by virus plaque assays. Virus reactivation was confirmed in ACV- treated HSV-1 quiescent cells by examining cell lysates for virus plaque forming units. Four days post infection of ACV-treated cells, culture medium was removed and replaced with medium containing TSA. Supernatant fluids from cultures treated with TSA showed virus production in plaque forming assays on Vero cells. Media from both lytically infected cultures and TSA reactivated cultures contained productive virus; however, media from latently infected cultures did not show the presence of infectious virus. Treatment of L929 cells with ACV 2 hours after infection with HSV-1 induced a quiescent effect better than treatment of the cells with AVC 24 hours before infection, because higher cell densities survived. As expected quantitative real-time polymerase chain reaction (qPCR) analysis of HSV-1 transcripts showed about one fold increase in Latency Associated Transcript (LAT) and a decrease in the lytic cycle infected cell protein (ICP0) in ACV-treated HSV-1 infected L929 cells at 16 hours post infection as compared with the untreated (open full item for complete abstract)

Committee: Nancy Bigley Ph.D. (Advisor); Barbara Hull Ph.D. (Advisor); F.Javier Alvarez-Leefmans M.D., Ph.D. (Committee Member) Subjects: Immunology; Microbiology