ItemViral Tool Development for Investigations of Learning and Memory(2018-08) de Solis, Christopher A; Ploski, Jonathan E.Developing new viral tools to investigate biological and behavioral phenomena is important to push neuroscience research to new avenues that were once limited by expensive and time consuming transgenic and knockout rodent models. This dissertation is a collection of experiments that outline the development and optimization of several viral vector systems for application of studying a gene’s function in the brain and the role it plays in behavioral phenomena. First, I show that knockdown of a gene’s transcript using short hairpin RNAs (shRNAs) delivered to neurons using adeno associated virus (AAV), is toxic to neurons and results in an impairment of Pavlovian auditory fear conditioning. Next, I outline the development of a doxycycline dependent CRISPR/Cas genome editing system for knockdown of genes in the brain using AAV as an alternative to gene knockdown with shRNAs. I then examine the efficiency of several AAV serotypes for their ability to function in a specific cell type, inhibitory neurons. Next, I sought to look for important genes that might be potentially important for memory consolidation in the hippocampus, with respect to transport of mRNA transcripts to the distal ends of dendrites of dentate gyrus granule cells following the induction of long-term potentiation (LTP). I found that Arc (Activity related cytoskeletal protein) mRNA was the most present in the dendrites following neuronal activation compared to all other known transcripts in the rat genome. Interestingly, another gene that was highly upregulated was an unprocessed microRNA (pri-miRNA), pri-miRNA-132. Finally, I use lentiviral vectors to investigate the role of GluN2B, an NMDA receptor subunit, in the updating of strong memories and found that increasing the level of GluN2B within the mouse basal and lateral complex of the amygdala (BLA) allows for the modification of an existing strong fear memory via reconsolidation, a process typically not initiated in stronger memories. ItemSeeking Refuge: Analysis of Deterrence Policies and Formal Rights(2018-05) Verma, Shaivya; 0000-0003-3746-2543 (Verma, S); Clarke, Harold D.Over the last twenty-five years, convergence towards deterrence policies has increased in both traditional and new asylum granting countries. After the breakup of the Soviet Union, the rapid increase in the number of people seeking refuge led countries adopt deterrence measures regarding refugee rights. The deterrence literature has identified a strong convergence among refugee-receiving states to adopt more and more preventative measures including restrictions and reduction of refugee rights, which may include removal of formal rights, such as Germany reforming its constitution in 1992 and removing absolute right to asylum. This growing body of scholarly literature in forced migration has sought to understand the effect of the rights and welfare policies on destination choice of refugees or forced migrants, but the research is limited to developed or OECD (Organisation for Economic Co-operation and Development) countries. This research aims to expand the existing research of refugees’ rights and constitutional protections to global countries. In addition, this research analyzes individual-level behavior through a field-work conducted on African refugees in India. First, I identify seven constitutional rights important for protecting forced migrants: the right to seek asylum, the right to seek refuge, alien/non-citizen freedom of movement, gender equality, racial equality, freedom of religion, and writ of habeas corpus. Results from a large dyadic panel from 1993-2014 show the constitutional right to seek asylum, gender protection, and race/nationality protection lead to more inflow of refugees in a country. Second, I examine the factors that lead countries to adopt deterrence policies and to which extent these domestic deterrence policies affect the destination choice of refugees. Results from a large panel dataset from 1997-2014 shows significant effect of the convergence of deterrence policies in countries that lie within a region. I do not find evidence that increase in the inflow of refugees in a county have any effect on the adoption of deterrence policies. The results are supported by the analysis in step two, where I find highly significant evidence that refugees are more likely to go to the contiguous countries and are impacted by the presence of social networks. Next, I do not find any effect of the number of contiguous conflict-affected countries on the adoption of restrictive policies. The results in the second part of the dissertation indicate that most refugees take refuge in neighboring countries, as most refugees do not reach developed countries that adopt more restrictive deterrence policies, especially in regard to the detention policies. The paper also indicates that deterrence policies work but as convergence builds they stop having a deterrent effect. Lastly, most studies use aggregate level data analysis which provides important insights but it is ultimately inappropriate for assessing individual level choices. I extend rational-choice theory to complement refugee-centered approach. The approach refines ‘micro-macro’ linkage. I study individual-level behavior arguing that forced migrants are not bogus and move to a place where they feel safe along with assessing the present policies and living situation in India. For the paper, I interviewed 155 African refugees and asylum seekers living in India. Using both quantitative and qualitative analysis, I find that the forced migrants take refuge in India due to many factors such as stable political conditions, social networks, role of agents, and for health and education purposes. I also find that forced migrants feel discriminated in India due to their skin color. ItemPrediction of Individualized Risk of Contralateral Breast Cancer(2018-05) Chowdhury, Marzana; Choudhary, Pankaj K.; Biswas, SwatiWomen diagnosed with cancer in one breast are increasingly choosing to remove their other unaffected (contralateral) breast through a surgery called contralateral prophylactic mastectomy (CPM) to reduce the risk of contralateral breast cancer (CBC). Yet a large proportion of CPMs are believed to be medically unnecessary because the risk of CBC has, in fact, gone down substantially mainly due to availability of effective therapies for breast cancer (BC), which have a preventative effect on the contralateral breast. Thus, this dramatic rise in the rate of CPMs is a particularly disturbing trend. Research shows that many BC patients tend to substantially overestimate their CBC risk. Although CPM reduces the risk of CBC, there is no convincing evidence that it prolongs survival. The surgery also has a significant number of side effects and can have an adverse effect on a woman’s health and well-being. Thus, there is a pressing need to educate patients effectively on their CBC risk. For this task, physicians need a statistical model for risk prediction of CBC based on patient’s personal risk factors. This dissertation is focused on filling this critical need. Although several risk factors for CBC are well established in the literature, one factor that is relatively less well-studied is mammographic breast density. This factor has come to the attention of the scientific community only recently and, in particular, it has been shown that increased breast density is a strong risk factor for first BC. Thus, it is of interest to study if it is associated with the risk of CBC as well. To this end, first we studied the relationship between breast density and CBC by analyzing data from Breast Cancer Surveillance Consortium (BCSC), which is a large population based source consisting of seven cancer registries across the US. We found that breast density is an independent and significant risk factor for development of CBC. In particular, breast density has a dose dependent effect on the risk of CBC, with increased breast density associated with increased risk. Next, we developed a CBC risk prediction model using data from BCSC and also Surveillance, Epidemiology, and End Results, another large population based source. We explored numerous potential risk factors for inclusion into this model. The final model consists of eight risk factors — age at first BC diagnosis, anti-estrogen therapy, family history of BC, high risk pre-neoplasia, estrogen receptor status, breast density, type of first BC, and age at first birth. Combining the relative risk estimates of these factors with the relevant hazard rates, our model, named CBCRisk, projects absolute risk of developing CBC over a given period. Finally, we validated CBCRisk on clinical datasets from the MD Anderson Cancer Center and Johns Hopkins University. We computed the relevant calibration and validation measures, and found that the model performs reasonably well for both datasets. With independent validation, CBCRisk can be used confidently in clinical settings in counseling BC patients by providing their individualized CBC risk. In turn, this may potentially help alleviate the rate of medically unnecessary CPMs. ItemTesting the Dark Sector Versus Modified Gravity Models in Cosmology(2018-08) Lin, Weikang; 0000-0003-2240-7031 (Lin, W); Ishak-Boushaki, MustaphaThis dissertation studies cosmological and astrophysical tests of gravity theories and the dark sectors. We focus on three tests. All of them are promising for future observations. The first test is about tensor-mode parameterization. While scalar-mode parameterization has been extensively studied, tensor-mode parameterization requires further investigations. This dissertation extends some previous work in the literature, and studies some physically motivated parameterization schemes, the current observational constraints, the future constraint forecast as well as the impacts on inflation consistency relation. The second test is based on consistency tests. The idea is to compare constraints from different observations and check the consistency of a model. This dissertation introduces a novel measure, called the index of inconsistency (IOI). It is a simple and effective measure. We proposed a procedure based on IOI to test (in)consistencies of multiple observations. The difference between this consistency test and the first one is that we do not assume all data are correct. In fact, our procedure allows us to find observation outliers or the breakdown of the model. The third test is about a phenomenological difference between modified gravity and dark matter. We studied properties of the faintest galaxy system in our local group, called the ultra-faint dwarf galaxies. We found a loss of correlation between their luminosity and stellar velocity dispersion. This does not favor the modified gravity hypothesis. ItemIdentifying Differences in the Neural Correlates Underlying Semantic and Syntactic Development(2018-05) Schneider, Julie M.; Maguire, Mandy J.Language comprehension requires millisecond level processing of semantic and syntactic information, yet children seem to integrate and comprehend all of this information with relative ease. Although this is done effortlessly, developmental differences exist in the speed by which children process speech. By understanding how variation in the developmental time-course of semantics and syntax may contribute to individual differences in language comprehension, we may lay a foundation to better understand how language develops in atypical populations. This study uses electroencephalography (EEG) to investigate how early school-age children, late school-age children, and adults process semantics and syntax in naturally paced sentences. Children ages 8-9 years, 12-13 years, and adults listened to semantically and syntactically correct and incorrect sentences and were asked to complete an acceptability judgment task. When processing a semantic error, there were no developmental differences in the N400; however, increases in theta, related to semantic processing, were greater for 8-9 year olds than 12-13 year olds and adults. These findings suggest that the N400 may be too gross a measure to identify more subtle aspects of semantic development that are ongoing in early school-aged children. For the syntactic task, errors resulted in a larger P600 and greater beta decrease than correct sentences, but the location of the P600 and the amplitude of beta decreases differed as a function of age, suggesting specialization of syntactic skills is ongoing through adolescence. Taken together, the findings from the current study suggest that the neural substrates underlying semantic processing appear to reach adult-like levels at a younger age, while syntactic skills develop over a protracted time course to support comprehension of natural language. ItemNovel Sensing Approaches towards Ultimate MEMS Sensors(2018-05) Kumar, Varun Subramaniam; Pourkamali, SiavashWithin the past few decades, several micro and nano-electromechanical (MEMS and NEMS) accelerometers, magnetometers and vibration sensors utilizing various actuation and sensing mechanisms have been developed and demonstrated. These sensors are integral to various geographical, industrial, military, environmental and biomedical applications. Although these sensors based on MEMS technology have been successfully commercialized and are widely used, this dissertation focuses on novel approaches to enhance the performance of such sensors drastically. In most cases for the MEMS accelerometer, the large power consumption of MEMS sensors is attributed to the analog front end needed for reading, processing, and analog to digital conversion of the sensor output, which is typically responsible for most to all the power consumption of the whole sensor. The proposed effort in this dissertation aims at development of a new class of digitally readable MEMS accelerometers allowing significant power reduction by eliminating the need for the analog front-end. Conventional magnetometers that offer high sensitivities for fields smaller than a few nT’s are not MEMS compatible and cannot undergo miniaturization. MEMS Magnetometers have an edge over conventional counterparts due to their unique features such as small size, low cost, lower power consumption and simplicity of operation. Such properties offer unrivalled advantages, especially when it comes to medical applications, such as magneto-encephalography, where compact arrays of ultra-sensitive sensors are desirable. This dissertation demonstrates ultra-high sensitivities (noise floor in pT/√Hz) for a Lorentz force resonant MEMS magnetometer enabled by internal-thermal piezoresistive vibration amplification. A detailed model of the magneto-thermo-electro-mechanical internal amplification is also developed and studied. Frequency modulation of a Lorentz force MEMS magnetometer for enhanced sensitivity using a leverage mechanism has also been explored. Currently, no low cost, low power, and compact vibration sensor solution exists that can provide frequency distribution data for the measured vibrations This dissertation implements and characterizes building blocks of a low-power miniaturized vibration spectrum analyzer with a resolution of 1mg over a wide frequency range (0-10kHz) using an existing Texas Instruments CMOS process, without adding any complex post processing fabrication steps. ItemIndian Association for the Cultivation of Science: Mahendralal Sircar and His Science, Morality, and Nationalism(2018-05) Ramanath, Sumathi; Gossin, Pamela S.Mahendralal Sircar (1833 – 1904) is known as a prominent homeopathic doctor and the founder of the Indian Association for the Cultivation of Science (IACS) in 1876, but scholars rarely refer to his role in promoting scientific studies as a nationalist endeavor. In this dissertation, I trace Mahendralal Sircar’s life and analyze how his views of science informed his work and how his IACS changed the course of scientific education and practice in India. While a recipient of the emerging Indian nationalism, the IACS changed the nature of Indian nationalism. I begin by highlighting the influence of Raja Ram Mohun Roy and his vision of monotheism, based on the Indian Vedanta, on the scholars and reformers of early nineteenth-century Bengal. Roy’s view of religion, science, and nationalism can be traced in the writings of Mahendralal Sircar, especially in his article “On the Desirability of the Cultivation of Sciences by the Natives of India” (1869). In this article, Sircar prescribes the creation of a scientific institute to influence moral growth and combat Indian idolatry and apathy. Additionally, Sircar wanted the institute to be funded and managed by Indians; its purpose would be to produce science-literate natives, making it a nationalistic endeavor that promoted the growth of the country. Next, I analyze the rhetoric that Sircar used to mobilize the natives to fund and participate in his Institute. He often referred to India’s enlightened past and hinted at the latent potential of the natives to create interest in Indian regeneration. Despite his hope for the future, Sircar had to operate within the British colonial system. I analyze his writings to reveal a conciliatory tone that Sircar had to adopt towards the British government. He carefully balanced supplicating the colonial apparatuses with inspiring natives to agitate for scientific autonomy. Using the Annual Reports of the IACS, I delve further into Sircar’s methodology for mobilizing the wealthy and landed elites toward his cause. Their money and participation was important to the foundation, upkeep, and development of the IACS. Finally, I enumerate how the IACS changed the face of scientific education in India. Sircar’s emphasis on the theoretical and practical education in science was a paradigm shift that produced scientific scholars, a scientifically literate society, and forced the established colleges and universities to change their science curriculum. Sircar foresaw the independence of India and insisted on Indians learning to be autonomous. His IACS gave Indians the first generation of scientists who were instrumental in building a nation in a post-independence era India. ItemWhat Drives Online Citizen Journalism in Malaysia? A Reasoned Action Model Approach(2017-12) Guynes, Del; Lee, Angela M.Citizen journalism is a global phenomenon that manifests in a variety of ways, depending on the political environment and extent of media freedoms. In Malaysia, it appears that citizen journalism has, over the past twenty years, contributed significantly to the rise of public discourse of opposition to some of the policies and behaviors of the ruling political party, the majority seat holder in Malaysia’s parliament since its independence from Great Britain in 1957. That majority in parliament has grown precariously thin, with the most recent national elections seeing almost 40% of the seats going to the opposition—which, in fact, actually won the popular vote. Until now, a theoretical basis for evaluating the behavioral reasons underlying citizen journalism has not appeared in the research in any context, thereby precluding an understanding of beliefs and perceptions that could lead to behavioral interventions that might encourage greater Malaysian participation in online journalism. To fill this gap, this dissertation takes the Reasoned Action Model (RAM) approach, a theoretical framework that has primarily been useful when examining health behaviors, and applies it to online citizen journalism in Malaysia. The dissertation employs an OLS multiple regression analysis for data gathered from an online survey (N = 2,020) that explores modal salient beliefs about factors that influence participation in citizen journalism in the Malaysian context. The RAM demonstrates an effective theoretical basis for evaluating drivers of participation in citizen journalism, exposing several key predictors of intention to participate, which include having the capacity to participate, possession of a smartphone, feeling satisfaction, and influence of friends, NGOs, and boyfriends/girlfriends, among others. Based on the findings, there are behavioral interventions that might positively influence the beliefs that underlie modal variables, with a view toward increasing intention to report online one’s views of government policies and elected officials. ItemFabrication of Polylactide Nanocomposite Filament Using Melt Extrusion and Filament Characterization for 3D Printing(2017-05) Jain, Shrenik Kumar; Tadesse, YonasFused deposition modeling (FDM) technology uses thermoplastic filament for layer by layer fabrication of objects. To make functional objects with desired properties, composite filaments are required in the FDM. In this thesis, less expensive mesoporous Nano carbon (NC) and carbon nanotube (CNT) infused in Polylactide (PLA) thermoplastic filaments were fabricated to improve the electrical properties and maintain sufficient strength for 3D printing. Solution blending was used for nanocomposite fabrication and melt extrusion was employed to make cylindrical filaments. Mechanical and electrical properties of 1 to 20 wt% of NC and 1 to 3 wt% of CNT filaments were investigated and significant improvement of conductivity (3.76 S/m) and sufficient yield strength (35MPa) were obtained. Scanning electron microscopy (SEM) images exhibited uniform dispersion of nanoparticles in polymer matrix and differential scanning calorimetry (DSC) results showed no significant changes in the glass transition temperature (Tg) for all the compositions. Perspective uses of this filament are for fabrication of electrical wires in 3D printed robots, drones, prosthetics, orthotics and others. ItemMulti-Platform Search-Based Advertising(2017-05) Zia, Mohammad; Rao, Ram C.This dissertation studies three problems in the context of multi-platform search-based advertising. “Search-based advertising” refers to the type of advertising that is initiated by a customer’s search activity. It includes, but not limited to, Google and Bing’s keyword advertising, Amazon and eBay’s sponsored links, and Expedia and Priceline’s targeted ads. I explore strategic interactions of three different agents in this environment: consumers, advertisers and search platforms. The first part of the dissertation analyzes advertisers’ bid coordination across platforms. I develop a model in which consumers repeatedly use two search platforms, and advertisers compete for advertising spaces in these platforms. I find that advertisers’ may optimally coordinate their bids across platforms such that they are assigned to a prominent position in one platform and a less prominent one in the other. The second part of this proposal investigates advertisers’ budget allocation across platforms when they have limited online advertising budgets. The focus of this essay is what fraction of budget an advertiser should assign to Google versus Bing. We find that the degree of heterogeneity in budgets is an important factor influencing advertisers’ decision. In particular, if budgets are far away, it is optimal for them to allocate their budgets exactly proportional to platforms’ traffic, e.g. 20% to Bing and 80% to Google. If budgets are close, on the other hand, advertisers specialize by allocating relatively higher fraction of budget to one platform and lower fraction to the other. Finally, the third part examines the profitability of search advertising when advertiser and host of the ad are direct competitors, i.e., they both sell a similar product. For example, Wal-Mart hosts banner ads for TVs from Sears to customers searching for TVs on Walmart.com, risking a loss of customers in exchange for the commission. I explore whether and under what conditions allowing competitor advertising in one’s store may be a beneficial strategy. I find that hosting competitor ads can mitigate price competition and boost profits of firms if the advertising firm pays a high enough commission on the customer traffic it receives through such ads. This can explain why Expedia, for example, provides a link to its own customers encouraging them to compare prices with Priceline.com, its direct rival.