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SURFACE PHYSICS OF NICKEL NANOPARTICLES ON GOLD
No full textAbstract: The study of nanoparticles involves structures and processes that occur on the nanometer length scale, which often display unusual behavior compared to their macroscale counterparts. In this thesis, we study Ni nanoparticles grown on Au(111). The Au(111) surface forms the herringbone reconstruction that provides a template for the periodic growth of ordered Ni nanoparticles. The Ni nanoparticles grow radially until a fractional surface coverage of about 0.3 monolayers (ML), after which, subsequent Ni atoms contribute primarily to a second layer. In this thesis we report on the surface physics of these Ni nanoparticles grown on Au(111) substrates with several different experimental techniques. Surface resistivity, measurements can detect the presence of small numbers of adsorbates, and grant insight into their morphology and interactions. It arises from the diffuse scattering of conduction electrons off adsorbates, and there is typically a linear relation between the increase in resistivity of the substrate and the number of adsorbates in direct contact with the substrate. By growing in ordered clusters, the Ni nanoparticles break some assumptions of adsorbate-induced surface resistivity models, thus a non-linear dependence between surface resistivity and the size of the Ni nanoparticles was anticipated. Our results, however, show a linear dependence during first layer growth of the Ni nanoparticles. During second layer growth, above a fractional Ni coverage of about 0.3 ML, additional Ni atoms make no significant contribution to resistivity. Studies of CO adsorption to different surfaces can reveal otherwise hidden aspects of the surface. We investigate CO adsorption to Ni nanoparticles of different sizes grown on the Au(111) surface at 227 K with temperature programmed desorption (TPD) and Fourier transform infrared spectroscopy (FTIR). At this temperature, it is known through the literature and our measurements that CO does not bind to the Au surface. We find layer-dependent adsorption properties for CO binding to the Ni nanoparticles during first and second layer growth. For first layer Ni nanoparticle growth, we find normal CO saturation coverages of about 0.5 ML, but lower peak desorption temperatures than CO on pure Ni, and find CO primarily in the atop position. During second layer Ni growth, we find anomalously high CO saturation coverages near 1 CO/Ni, slightly higher peak desorption temperatures, but still primarily atop CO. Based on previous studies, we propose that in the first Ni layer, ligand effects from the Au substrate and possibly Au in the islands and strain due to the Ni/Au lattice mismatch affect the Ni-CO bonds. CO adsorption behavior on the two-layer islands is qualitatively explained by a decrease in Au nearest neighbors and the presence of a more expanded/corrugated structure.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Physics.Advisor: Roger Tobin.Committee: Peggy Cebe, Hugh Gallagher, and Carl Ventrice.Keywords: Condensed matter physics, Nanoscience, and Physics
The cardiac repair response of Xenopus laevis tadpoles to KillerRed-induced oxidative stress
No full textAbstract: The heart is an organ of vital importance and great fragility. In humans, damage to the heart leads to scarring, dysfunction, and heart failure. In contrast, amphibian hearts have heightened reparative abilities, and an understanding of how they accomplish this feat can lead to a greater knowledge of improving human heart health. We have developed a novel optogenetic model of heart disease in the Xenopus laevis tadpole, taking advantage of the unique ability of a genetically encoded photosensitizer, the KillerRed protein, to generate reactive oxygen species upon activation with green light. We show that KillerRed can be used to ablate tissues and developing organs in the X. laevis tadpole, and that when this method of damage is applied to the heart, it induces a phenotype mimicking cardiac stress in mammals. We demonstrate that partial dedifferentiation and proliferation of cardiomyocytes, mechanisms normally associated with cardiac regeneration, are activated in the X. laevis heart (a nonregenerative system) following KillerRed-induced damage, and that these mechanisms are regulated by different pathways than they are in organisms with fully regenerative hearts. Finally, we characterize the effects of alternate methods of activating KillerRed in the heart and show that activation by different light sources induces drastically different phenotypes. The data we present here show the unique nature of the Xenopus laevis cardiac response to oxidative stress, distinct from either mammals or organisms capable of full cardiac regeneration, and highlight this model system's importance in demonstrating an intermediate level of reparative and regenerative potential.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Biology.Advisor: Kelly McLaughlin.Committee: Stephen Fuchs, Michael Levin, Harry Bernheim, and Catherine McCusker.Keyword: Developmental biology
Urban Waterfront Revitalization and Open Space: A case of rezoning waterfront of Yong River in Nanning, China
No full textAbstract: Renovation of public open space on the urban waterfront is a unique part of the urban setting of many waterside cities. Urban waterfront revitalization is not just old city reconstruction and new zone development; it is also a balance between economic needs and the public's demand for access to the water. Waterfront revitalization is a phenomenon in Nanning, China. The Yong River offers main waterfront shorelines in Nanning's core urban area, which covers about 70 kilometers on each bank. The government is gradually emphasizing waterfront open space. A decision to convert undeveloped land, which consists of 50% of total waterfront area, into public space has been made and will result in an increase in public waterfront space from 10% to 20%. This research employs a case study method based on both qualitative and quantitative approaches, utilizing archival research, site observation and survey. The study details the current situation of Nanning's waterfront open space and then makes recommendations for how policy makers and urban planners in Nanning can balance public open space with other land uses in revitalizing their waterfront.Thesis (M.A.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisor: Penn Lloh.Committee: Sumeeta Srinivasan.Keyword: Urban planning
Functional analysis and therapeutic targeting of AKT isoforms in BRAF mutant melanoma
No full textAbstract: Despite recent advances, metastatic melanoma remains the deadliest form of skin cancer, and new therapeutic strategies are urgently needed. The PI3K/AKT pathway is known to promote tumor progression and metastatic dissemination in many cancer types, including melanoma. PI3K/AKT signaling is hyperactivated in many melanomas, often through loss of the negative regulator PTEN, which occurs in 12-20% of cases. PTEN loss cooperates with oncogenic BRAF to induce metastatic melanoma and leads to unrestrained activity of the PI3K effector kinase, AKT. The AKT family of serine/threonine kinases comprises three highly homologous isoforms (AKT1, AKT2, and AKT3) that are major effectors of the PI3K pathway, but despite their unique roles in other cancers, isoform-specific effects in melanoma have yet to be systematically interrogated. We performed shRNA mediated conditional knockdown and CRISPR/Cas9 gene editing of AKTs in a wide variety of human melanoma cell lines, as well as genetic ablation of each isoform in a BRAF-driven mouse model of melanoma. We reveal a role for AKT2 in promoting melanoma cell migration and invasion in vitro and find that AKT2 is required for metastatic seeding in vivo. Additionally, AKT2 specific depletion delays tumor growth and improves survival of mice with metastatic disease after tumor cell seeding, suggesting that AKT2 supports growth or survival in the metastatic niche. We propose several mechanisms whereby AKT2 may mediate these phenotypes, including via regulation of key epithelial-mesenchymal genes, promoting aerobic glycolysis, and responding to hypoxia. In contrast, we observe that the AKT1 isoform specifically promotes melanoma cell proliferation, and genetic ablation of AKT1 in melanoma prone mice prolongs overall survival. We also reveal that the AKT3 isoform may be important in UV-initiated melanomagenesis. Lastly, while non-specific pan-AKT inhibitors are used clinically to moderate benefit, their use is hampered by myriad off-target effects. To increase the efficacy of AKT targeting for clinical benefit, we endeavored to identify AKT isoform-specific substrate effectors that may be mediating differential phenotypes, and therefore potential targets for therapy. We also report efforts to use a tumor specific antigen to target a clinically relevant pan-AKT inhibitor to melanoma tumors in the mouse, and additionally test small molecule inhibitors that synergize with existing targeted therapies. In summary, our work moves toward establishing the contribution of AKT isoforms to melanoma, to improve therapeutic strategies and outcome for this devastating disease.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Genetics.Advisors: Phil Hinds, and Karl Munger.Committee: Philip Tsichlis, Charlotte Kuperwasser, and Alex Toker.Keywords: Genetics, Oncology, and Cellular biology
Engineered in vitro models for studying pulmonary fibrosis and infectious disease
No full textAbstract: Pulmonary fibrosis resulting in scar formation can be caused by exposure to aerosolized environmental contaminants, radiotherapy, chemotherapy and infectious disease (e.g., Tuberculosis). Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology and has a median life expectancy of 3 years after diagnosis. Treatments for IPF are limited (pirfenidone and nintedanib) and most lead candidate drugs identified in pre-clinical animal studies have failed human clinical trials. While animal models are useful for delineating fibrotic disease pathways, they do not accurately represent human IPF disease. Significantly, animal models (e.g., bleomycin) of fibrosis do not reproduce human fibroblastic foci (Hum-FF) formation, widely accepted as the pathological hallmark of human IPF disease. Human fibroblastic foci (Hum-FF) are important prognostic markers and both FDA approved treatments primarily target signaling pathways associated with myofibroblast cells found within these sites. Hence, replicating Hum-FF using model systems has the potential to improve our understanding of human IPF disease progression and treatment. Collagen-type I hydrogels, polyacrylamide hydrogels and fibrosis-on-chip systems have been used to model Hum-FF formation. However, current iterations of these systems are unable to successfully replicate the 3D complexity and biochemical composition of Hum-FF tissue. Thus, there is a need for advanced engineered in vitro models recapitulating 3D Hum-FF morphology with the capacity to apply biomechanical stimuli and mechanical tunability. We hypothesized that an engineered 3D fibroblastic focus (Eng-FF) model generated using silk fibroin dityrosine crosslinked hydrogels seeded with human pulmonary cells in a bioreactor would provide suitable tissue systems to model Hum-FF. The current dissertation evaluated silk dityrosine crosslinking in the presence of dopants (e.g., phenol red) towards establishing key variables, parameters required for 3D pulmonary cell encapsulation. Results from these studies showed that tyrosine containing amino acids and dopants including phenol red covalently crosslinked with the silk hydrogel framework, modulating crosslinking reaction times and hydrogel elastic moduli. The conclusion of this study marked identification of key parameters required for pulmonary cell encapsulation/culture and the fabrication of cytocompatible phenol-red tyrosine crosslinked hydrogels that could be used for in vitro pH sensing applications. Collagen-type I is the major ECM protein found within mature Hum-FF and dityrosine crosslinked silk-collagen-type I hydrogels were fabricated towards modeling Hum-FF. Characterization of pulmonary fibroblast encapsulated silk-collagen-type I hydrogel systems showed reduced fibroblast mediated collagen contraction compared to collagen-type I hydrogels, providing stable substrates for long-term in vitro culture of pulmonary cells. Silk-collagen-type I hydrogel systems exhibited superior mechanical tunability with the capacity to represent distinct normal and fibrotic disease states. Using customized Flexcell Tissue Train bioreactors and cellular seeding regime the Hum-FF pathology was successfully reproduced, and a thick stromal pulmonary fibroblast layer separated airway epithelial and microvascular endothelial layers. Fibroblasts and collagen fibers within Eng-FF tissues underwent parallel alignment with increase in culture period, accurately replicating Hum-FF cellular morphology. Eng-FF tissues can be used to model myofibroblast differentiation and long-term cultures resulted in a proto-myofibroblast phenotype and robust myofibroblast differentiation was induced by exogenous TGF-β1 cytokine. Pirfenidone abrogated TGF-β1 induced myofibroblast differentiation better than nintedanib at tested concentrations and Eng-FF tissues supported evaluation of myofibroblast phenotype following anti-fibrotic drug treatments. Eng-FF tissues could be used to model different facets of IPF disease and proof-of-concept studies showed replication of epithelial injury with the facile addition of bleomycin, and cellular recruitment to the FF could be studied by the perfusion of cells through the hydrogel microchannel. Towards future work, preliminary results were obtained towards fabricating silk-ECM hydrogels incorporating lung ECM proteins from normal and pathological disease states including ECM proteins from human IPF lungs and murine tuberculosis granulomas. In summary, the current dissertation evaluated tyrosine crosslinking of dopants and ECM proteins with silk fibroin proteins towards creating in vitro culture systems for modeling normal lung physiology and disease. The dissertation affirms the feasibility of utilizing silk-ECM hydrogels for modeling lung disease with the successful creation of a 3D in vitro engineered fibroblastic focus model using human cells that reproduces Hum-FF pathology and cellular phenotype.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Biomedical Engineering.Advisor: David Kaplan.Committee: Gordana Vunjak-Novakovic, Lauren Black III, Gillian Beamer, and Bree Aldridge.Keywords: Biomedical engineering, Bioengineering, and Biology
When to look at maps in navigation: metacognitive control in environment learning.
No full textAbstract: People learn environments through direct experience with the environment and/or through map study. Further, the different perspectives taken while learning an environment influence the knowledge acquired. After all, different information about an environment is readily available through route (e.g. by navigation) and survey (e.g. with maps) perspectives. Having a choice between direct experience and map use, or between different perspectives, suggests a role of metacognitive control in environment learning. That is, when in a new environment, learners may exercise metacognitive control by selectively choosing and implementing specific learning strategies, such as switching between perspectives. Strategy choice may depend on specific constraints, such as perspective, range of view, or amount of time to learn (to name a few). For example, people may check a map (e.g. on smartphones or GPS devices) to complement developing route knowledge. The present review discusses the role of metacognition in environment learning and outlines new directions for research to bridge these fields by examining how strategic metacognitive control over perspective switching affects environment learning. Such explorations can inform real-world environment learning and navigational aids design
The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation.
No full textBackground and aims: Endothelial surface glycocalyx shedding plays a role in endothelial dysfunction and increases vessel wall permeability, which can lead to inflammation and atherogenesis. We sought to elucidate whether a high fat diet (HFD) or disturbed blood flow conditions, both of which are atherogenic risk factors, would contribute more detrimentally to pre-atherosclerotic loss of endothelial glycocalyx integrity and vascular inflammation.Keywords: Glycocalyx, Endothelial dysfunction, Atherogenesis, Inflammation, High fat diet, Disturbed blood flow.Springer Open
Diegetic presence in cinematic virtual reality.
No full textA unique feature of cinematic virtual reality (CVR) as a medium is its attempt to produce in its viewer a sense of diegetic presence: authors of CVR use techniques to promote in the viewer a feeling that she is within the story-world represented by CVR, as mediated through the head-mounted display. This poster represents the findings from my preliminary research in the summer of 2018. I argue that CVR authors' priority of presence preservation is heavily shaping the aesthetics of this medium. I then discuss modes of diegetic presence, and the particular experiences these modes afford. This work will be continued in my thesis research, beginning in Spring 2019. Submitted in partial fulfillment of the grant requirement of the Tufts Summer Scholars Program
Firefly Conservation: Assessing Threats and Risk Factors in North American Firefly Species.
No full textSummer Scholars 2018 Research Project. Supervised by Dr. Sara Lewis and Dr. Michael Reed. Submitted in partial fulfillment of the grant requirement of the Tufts Summer Scholars Program
Fortification of rice improves dietary adequacy and equity of nutrient intake in Nepal: evidence from a modelling approach.
No full textThis presentation was from 6th Annual scientific Symposium in Nepal