University of Maryland, Baltimore County
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Visualizing Motional Correlations in Molecular Dynamics using Geometric Deformations
No full textCovariance matrices are used by molecular researchers to represent motional correlation. An allosteric effect is when a change at one site of a molecule affects a distant site. Allosteric effects can be important for studying the effectiveness of new drug molecules. Studying motional correlation is a way to discovering how the change from the source site affects the target. By improving our ability to analyze these correlated relationships, It may be possible to develop new medications to combat deadly diseases such as Hepatitis C. We present five visual techniques which represent this matrix data on rendered three-dimensional molecular visualizations. We provide a new way to view clusters of correlated residues and paths of allosteric activity. These techniques give us a brand new way of investigating the presence of motional correlations in complex disease molecules. We compare and contrast each of these techniques to determine which are the most useful for representing covariance data
The Influence of Neural Stem Cells on the Physical Properties of Poly(Ethylene Glycol) Hydrogel Scaffolds
No full textImprovement of nerve repair therapeutics relies on a clear understanding of neural response, including how neurons interact with their extracellular environment. Various cell types, including neurons, are known to secrete extracellular matrix molecules. Current systems for neural stem cell (NSC) encapsulation are generally focused on directing cell differentiation, yet typically overlook cellular remodeling of their environment, which could have dramatic effects on multiple cell responses including viability, proliferation and differentiation. Preliminary studies suggested that NSCs actively sense and remodel their environment when encapsulated in a hydrogel scaffold as indicated by an increase in gel stiffness, decrease in swelling ratio and slower degradation time. Therefore, the purpose of this study was to monitor gel degradation time as well as molecule secretion by NSCs. Our work not only demonstrated that gel degradation time is slower when encapsulated with NSCs, but also that NSCs alter the sulfhydryl concentration in the cell culture medium
European Union Conditionality as Impetus for Improved Health Systems in Croatia
No full textBackground: This dissertation explores how the "Europeanization" of Croatia has affected the Croatian health system and its stakeholders. Supranational organizations, such as the European Union, have the potential to harness the enthusiasm of candidate nations and to influence domestic policies of member states by imposing economic sanctions on countries that fail to comply with international health and human rights standards and by offering economic incentives to countries that do comply. Economic stability attendant to EU membership encourages nations to work together to overcome differences and to adopt social policy reforms by providing a tangible and imminent incentive. In this study, the researcher uses qualitative methodology to examine the evolution of Croatian health policy in the context of EU integration. Hypothesis: As a result of both active and passive leverage, the incentive of European Union (EU) membership has been the critical element responsible for health policy reforms in Croatia from 2003 to 2008. Methods: The methods employed in this descriptive case study are three-fold: historical process tracing, manifest content analysis of key documents in Croatian health policy and directed content analysis of stakeholder interviews. The content analysis included ten documents, consisting of legislation and strategic health policy reform initiatives. Sampling for the informant interviews was purposive and phenomenological. A total of thirty interview subjects were identified based upon authorship of documents discovered in the course of the literature review and through blanket emails to government ministries, NGOs, and other groups associated with health policy-making in Croatia. Based upon the 2001 Croatian Census Data, the sample was drawn from each of the four regions of Croatia: Dalmatia, Istria, Central Croatia, and Slavonia to represent a diverse sample based upon the following criteria: population size, geographic region of the country, ethnic diversity, and the severity of conflict/number of ethnic minorities present. The interview questionnaire consisted of ten questions designed to assess stakeholder experiences and attitudes about changes to the Croatian health system over the past decade. Results: Attitudes of stakeholders both shaped and reflected the priority areas and concerns that Croatian health policy reforms have sought to address. With respect to health policy priorities, and obstacles to achieving them, a general consensus exists between EU policy-makers, Croatian policy-makers, and the sample of stakeholders in the Croatian health system selected to participate in this dissertation research. Among the interview subjects, priorities fell into five broad categories: cost, efficiency, quality, access, and mentality. Three out of five of these priorities (Quality, Access, and Mentality) also appear in the health system policy agendas for Croatia and the EU. Document analysis revealed that none of the health policy reforms in Croatia were the result of active leverage during the formal harmonization negotiation process, but that the EU did have a strong influence on Croatian health policy in the form of passive leverage. However, the EU did apply active leverage in other economic and social policy areas and stakeholders believed that the effects of these reforms on social and economic conditions in Croatia have been largely positive. As a result, population health in Croatia may benefit from these economic and social policy changes as they affect social determinants of health. This phenomenon, latent active leverage, describes the indirect effects of active leverage on population health resulting from economic and social policy changes which were not specifically targeted health policy reforms. Conclusion: The incentive of EU membership has been the critical element responsible for health policy reforms in Croatia from 2003 to 2008, but primarily as a result of passive leverage. The EU has tremendous, and largely underutilized, potential to promote health system improvement by providing economic incentives to candidate countries as part of the integration process
Analyses of assembly and functional defects in the ribosome of L4 and L22 mutant Escherichia coli strains
No full textThe ribosome is a complex macromolecule consisting of RNA and protein subunits that is responsible for translating the genetic code and protein synthesis. Within its large subunit, the exit tunnel exists as a conduit for nascent peptides to traverse before reaching the cytoplasm or membrane translocon. The tips of the extended loops (also called tentacles) of two proteins, L4 and L22, contribute to the surface of the narrowest portion of Escherichia coli's exit tunnel. Mutations in the tentacles of the L4 and L22 proteins promote resistance to a class of antibiotics referred to as macrolides. Although the mutant strains have the advantage of growing in the presence of the antibiotic, erythromycin, they have the disadvantage of growing slower than the wildtype. The decreased rate of growth may be a reflection of structural changes within the 23S rRNA component of the large subunit induced by structural changes in L4 and L22, which in turn result in defects in ribosomal assembly and/or peptide synthesis. My research involved determining whether the reduced growth rate can be attributed to the rate of peptide bond formation in the peptidyltransferase (PT) center and/or the reduced efficiency of ribosomal assembly. I used the peptidyltransferase assay on total ribosomes and purified subunits to evaluate the effect of the L4 and L22 mutations on ribosomal function. A decrease in PT activity was observed amongst all mutants. Analyses of Variance and Tukey's honestly significant difference test indicated that the differences between the wildtype and the mutants were statistically significant. Additional statistical analyses revealed a strong positive correlation between my PT results and Zaman's data in which she used the β-galactosidase induction assay to show a decreased rate of peptide chain elongation amongst the mutants. I also used sucrose gradient analyses and primer extension to evaluate the effect of L4 and L22 mutations on ribosomal assembly and processing. An abnormal peak was observed between the 30S and 50S peaks in the selected mutants. Increased levels of precursor 23S rRNA were observed in the primer extension results of all mutants. My results further substantiate the important roles that the L4 and L22 proteins provide in the function and assembly of the ribosome
Investigating a role for NXN and its interaction with ciliary protein IFT88 in planar cell polarity signaling
No full textThe human brain is considered the most complex organ. The early stages of brain development may perhaps be the most crucial time in the brain's formation as neural tube defects occur very early in pregnancy if the neural tube does not close completely. I am interested in the early events that shape the central nervous system, namely: the cell behaviors that shape the neural tube, the precursor of the brain and spinal cord. A signaling pathway called planar cell polarity (PCP) mediates proper cellular behaviors in many tissues, including the developing neural tube. There is an ongoing controversy as to whether cilia mediate PCP signaling during neural tube formation and other developmental processes. Evidence that ciliary proteins are required for neural tube formation stems from the observation that disruption of multiple genes implicated in ciliogenesis results in delayed or blocked neural tube formation. Nevertheless, whether impaired ciliogenesis prevents proper PCP signaling remains unknown. Using a bioinformatics approach, the Kann laboratory recently identified the novel PCP pathway component Nucleoredoxin (Nxn) as a putative bindig partner of the ciliary protein IFT88. Nxn therefore provides a molecular entry point with which to explore the interaction between cilia and PCP signaling. My thesis work centers on validating Nxn as an IFT88 binding partner and testing the predictions that depletion of Nxn should cause similar neural tube defects as those observed in PCP mutants and Nxn should localize to cilia where IFT88 is also enriched. This research lays the framework for future studies on mechanisms of cilia-PCP interactions
Burden of Care: Women's Environmental Responsibility in U.S. Popular Media
No full textLifestyle media have the power to impact women's understanding of environmentalism and what it means to be a woman environmentalist in the United States. Surveying popular women's lifestyle media sources in the U.S., I conducted a discourse analysis of various types of environmental narratives, seeking to understand how this media defined environmentalism and the environmentalist, and what the implications of these definitions might be for American culture. I tracked the intersections of gender, environmentalism, and mass media from an interdisciplinary, feminist perspective, drawing on theorists' conceptions of media framing to draw out recurrent themes. In surveying a range of lifestyle media sources, I found that media framing of environmental narratives leveraged the American cultural value of individual agency, focusing on the power of private sphere activities to foment change, and using class distinction and educational markers to link environmentalism to sophistication among one's peers. Media often framed environmental narratives in terms of motherhood archetypes, linking environmentalism to maternalism and implying that mothers bore unique social responsibilities for environmental action. Finally, environmental narratives in lifestyle media appeared to reflect an underlying effort on the part of media to depoliticize environmentalism, promoting environmentalism as a mainstream value and portraying women environmentalists as the embodiment of traditional American cultural values. Overall, I found that environmental narratives in lifestyle media framed women's environmental responsibilities in terms of long-standing, static conceptions of womanhood and motherhood, and similarly gendered notions of the social responsibility to care for one's family or community. Moreover, environmental narratives seemed likely to reinforce hegemonic cultural conceptions of women's identities and social agency. These narratives therefore have the potential to fuel existing gender inequities tied to social expectations for the division of domestic labor. Despite these findings, there has been a general dearth of scholarship focused on the implications of such narratives, and the portrayal of women's environmentalism in popular mass media. The construction of environmentalism in women's lifestyle media will thus benefit from an analysis based in a feminist perspective, providing a basis for future scholarship on the cultural implications of saddling women with the burden of environmental care
The role of the circadian clock gene LUX ARRHYTHMO in regulating innate immunity in Arabidopsis
No full textEach year pathogen-caused plant diseases are responsible for massive losses in crop yields and have tremendously impacted global economy. To more effectively fight off these diseases it is imperative to better understand how plants activate their immune responses. The circadian clock is the internal time measuring machinery that regulates many physiological processes of organisms. Recent studies from our and several other groups have demonstrated the roles of day-time components of the central oscillator of Arabidopsis biological clock, CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY),, in regulating defense responses. In this study I investigate the role of the night-time circadian clock component, LUX ARRHYTHMO (LUX), in defense control. Results from my experiments suggest that LUX plays a critical role in resistance to a virulent P. syringae strain but not two isogenic avirulent strains, suggesting a contribution of LUX in basal defense. Genetic analysis with a defense-sensitized acd6-1 mutant further revealed that LUX acts through salicylic acid-mediated defense pathway. This study demonstrates a role of an additional key component of the circadian clock in defense control, highlighting the importance of the circadian clock in regulating plant innate immunity
Experimental and Theoretical Investigation of Intratumoral Nanoparticle Distribution to Enhance Magnetic Nanoparticle Hyperthermia
No full textMagnetic nanoparticles have gained prominence in recent years for use in clinical applications such as imaging, drug delivery, and hyperthermia. Magnetic nanoparticle hyperthermia is a minimally invasive and effective approach for confined heating in tumors with little collateral damage. One of the major problems in the field of magnetic nanoparticle hyperthermia is irregular heat distribution in tumors which caused repeatable heat distribution quite impossible. This causes under dosage in tumor area and overheating in normal tissue. In this study, we develop a unified approach to understand magnetic nanoparticle distribution and temperature elevations in gel and tumors. A microCT imaging system is first used to visualize and quantify nanoparticle distribution in both tumors and tissue equivalent phantom gels. The microCT based nanoparticle concentration is related to specific absorption rate (SAR) of the nanoparticles and is confirmed by heat distribution experiments in tissue equivalent phantom gels. An optimal infusion protocol is identified to generate controllable and repeatable nanoparticle distribution in tumors. In vivo animal experiments are performed to measure intratumoral temperature elevations in PC3 xenograft tumors implanted in mice during magnetic nanoparticle hyperthermia. The effect of nanofluid injection parameters on the resulted temperature distribution is studied. It shows that the tumor temperatures can be elevated above 50C using very small amounts of ferrofluid with a relatively low magnetic field. Slower ferrofluid infusion rates result in smaller nanoparticle distribution volumes in the tumors, however, it gives the much required controllability and repeatability when compared to the higher infusion rates. More nanoparticles occupy a smaller volume in the vicinity of the injection site with slower infusion rates, causing higher temperature elevations in the tumors. Based on the microCT imaging analyses of nanoparticles in tumors, a mass transport model is developed to simulate nanoparticle convection and diffusion in tumors, heat-induced tumor structural changes, as well as nanoparticle re-distribution during nanoparticle hyperthermia procedures. The modeled thermal damage induced nanoparticle redistribution predicts a 20% increase in the radius of the spherical tissue region containing nanoparticles. The developed model has demonstrated the feasibility of enhancing nanoparticle dispersion from injection sites using targeted thermal damage
Photo-Assisted Electrochemical Detection (PAED) Following HPLC-UV for the Determination of RDX and Degradation Products
No full textContinuous efforts implemented by government agencies such as the United States Geological Survey (USGS) aim to manage and protect the integrity of the environment's natural resources. Moreover, emerging bioremediation technology requiring the use of microorganisms to destroy hazardous waste has effectively contributed to reducing the concentration of environmental contaminants. Of particular importance is the degradation of RDX in natural environments and subsequently, the accumulation of consequential degradation products in nature. RDX is the most frequently utilized nitramine explosive for mining, demolition and munitions purposes in the United States (US). Additionally, RDX has the potential to be degraded by microorganisms resulting in hazardous levels of harmful degradation products in soil and groundwater. The necessity for the detection of these particular degradation products is emphasized as a consequence of their recognized toxicity. In particular, cyclic N-nitroso degradation products of RDX have been recognized as potential mutagens. Photo-assisted electrochemical detection (PAED) following HPLC-UV is used to develop an analytical method qualified for the assessment of the degradation of RDX and formation of selected degradation products. The technique offers unique selectivity possessed by the photochemical reactor coupled to EC detection serving to eliminate the need for repetitive analysis using different column technologies. Furthermore, on-line sample pretreatment is developed and optimized specifically for the preparation of samples consisting of RDX and degradation products of RDX. On-line solid phase extraction (SPE) offers several advantages to conventional SPE including lower cost, reduced analysis time, and system compatibility for routine analysis. Analytical figures of merit determined for all target analytes using on-line SPE-HPLC-UV-PAED revealed detection limits in the sub part per billion range for RDX and degradation product MEDINA. Furthermore, the method was validated with the guidelines established by the Resource Conservation and Recovery Act in 1976, qualifying it capable for application in environmental fieldwork. As a result, the effectiveness of the method is exemplified in collaborative studies with the USGS in monitoring the degradation of RDX and formation of respective degradation products once the nitro explosive is subject to anaerobic microorganisms WBC-2 under controlled conditions
Multivariate Time Series Analysis of Physiological and Clinical Data
No full textThe complexity and volume of collected medical data is greater now than at any point in the history of medicine. Medical providers are expected to examine large volumes of data and identify correlations among parameters based on their own clinical experience to detect significant medical events or conditions. The information overload that providers may face may hinder the diagnostic process cite{heldt2006}. Most existing visualizations of the data to assist the provider in analyzing the information consist of a table or plot of values for a particular parameter as a function of time. Automated techniques for discovering these correlations not only may assist the provider in making a diagnosis but may help to identify hidden patterns within the data associated with specific medical conditions or events. Current visualization and machine learning techniques show promise for extracting this information. This dissertation presents three novel representations and two visualizations to assist in the analysis of multivariate time series data. It focuses on physiological and clinical data, in particular, because this type of data captures the complexity of a human being and thus the multivariate time series are more interdependent and better synchronized than most that measure the state of an entity. The three representations are the Multivariate Time Series Amalgam (MTSA), the Stacked Bags-of-Patterns (Stacked BoP), and the Multivariate Bag-of-Patterns (Multivariate BoP). Each provides an integrated, multivariate approach for representing multivariate time series data. An evaluation of the latter two techniques against two techniques that use univariate techniques of multiple variables, Ensemble Voting with Bag-of-Patterns and Multivariate Piecewise Dynamic Time Warping in six diverse datasets yields interesting insights into the classification of multivariate time series. The MTSA representation is the foundation for two visualizations - the MTSA Visualization and the Fixed Dual MTSA Visualization. These animated visualizations capture the rate of change of provider-selected parameters and the relationships among them. While both visualizations were created for the medical domain, they generalize to domains where multiple variables measure the state of an entity as a function of time. An evaluation of the Fixed Dual MTSA Visualization was carried out with 23 pediatric residents at Johns Hopkins University School of Medicine. The results indicate that the visualization merits further investigation for use as a diagnostic tool