VictorJuiz/thesis huggingface dataset:
Structural Characterization of Photoreceptor Complexes by EPR Spectroscopy
Keywords: EPR spectroscopy
GPCR
Photoreceptor
Rhodopsin
X-ray crystallization

Photoreceptor proteins are detectors that sense and respond to light signals in various organisms. In vertebrates, rhodopsin is the primary element of vision and is responsible for converting light to nerve impulses through a series of signaling events. In bacteria, however, a light-driven proton pump, bacteriorhodopsin, utilizes the energy of light to create proton gradients which leads to the generation of chemical energy. The goal of my thesis is to understand the molecular mechanism of these photoreceptors and their signaling complexes. Technological advances in protein crystallography in recent years have brought many outstanding results; however, not all samples are suitable for protein X-ray crystallography due to their heterogeneous and dynamic nature. First, I applied electron paramagnetic resonance (EPR) spectroscopy together with spin labeling techniques to study the conformations of visual arrestin upon its activation. In this study, I propose that visual arrestin only adopts a twist conformation when it interacts with light-activated rhodopsin. Second, I solved the crystal structure of a novel rhodopsin kinase and characterized its interaction with rhodopsin using EPR spectroscopy. Lastly, I solved the crystal structure of a cyanobacterial rhodopsin and determined its oligomeric states in detergent micelles with pulsed EPR techniques. Overall, I demonstrated that EPR spectroscopy is a powerful tool to study membrane protein complexes and it provides valuable information on protein structure and dynamics.
Millimeter-Scale Magnetically Actuated Robotic Tools for Surgery and Cell Manipulation
Keywords: cutting
magnetics
mechanisms
microrobotics
modelling
on-chip device

Small scale robots are precise end-effectors that can manipulate objects with a high degree of accuracy. Many surgical and on-chip tasks can be performed by manipulating these robots in their dedicated environments. Mobile untethered surgical robots are an attractive research area because of their ability to maneuver inside small and constrained environments and perform tasks that were previously considered infeasible. These robots enable us to make surgery minimally invasive. Surgeons can drill a hole in your skull and insert the tools inside the ventricles from where they can navigate their way to either cut or grasp tissue. Because these robots are too small for electronics and on-board power, they are often actuated remotely using magnetic fields as these field can penetrate most environments and are relatively safe for biological organisms. This makes them an ideal tool to use inside the human body and for on-chip applications. Magnetic tools can be developed and placed inside microfluidic platforms for cell manipulation such as sorting and stimulation. Both on-chip and mobile devices are explored in this thesis focusing on applications related to cell manipulation as well as surgical tools. Specifically, this thesis involves a discussion on the development of a pair of micro-surgical scissors for cutting of soft tissues as well as a magnetically oscillating beam that can be used to apply shear stress to cells and used for cell sorting purposes.
Modeling and Experimentation of Squeeze Film Dampers Considering Fluid Inertia, Film Cavitation and Design Features in Aircraft Engine
Keywords: Aircraft Engine
Squeeze Film Damper

Unbalance-induced vibration in aircraft engines is the major source of cabin noise and discomfort for passengers. One key component in attenuating the vibration level in an engine rotor is the squeeze film damper (SFD). The implementation of SFDs in high-speed turbomachinery increases the rotor stability and reduces the vibration amplitude at critical speeds. Despite the successful operation of SFDs in aero engines for decades, currently applied SFD models are not sophisticated enough to recognize unique features that affect damping performance. Development of an accurate and computationally efficient model has been an ongoing challenge. The object of this thesis is to develop SFD models that incorporate the fluid inertia, film cavitation, lubricant seals, and supply mechanism to provide a precise prediction of damper behavior at high operating speeds. To be specific, the fluid inertia is resolved by the momentum approximation method and perturbation method; film cavitation is formulated by the Elrod cavitation algorithm [1] and the linear complementarity problem method [2]; the effect of lubricant seals is addressed by the leakage flow at the seal groove for piston ring seals [3]; the supply mechanism is modeled by the flow interaction at the central groove. Moreover, the developed models are integrated into a rotordynamic system to estimate the critical speeds and vibration amplitudes. To accelerate the simulation time, a polynomial interpolation technique for SFD models is introduced to solve for the SFD forces under different operating conditions. Both the steady-state response and the frequency response are presented for an open SFD application. To validate the developed SFD models, an experiment for a single flexible rotor supported with two identical SFDs is executed. Displacements of both the central disk and support SFDs are measured to correlate the theoretical prediction. Some design and operation parameters including the film clearance and supply pressure are examined in the test to evaluate their effect. Results have shown excellent agreement in terms of the critical speed and vibration amplitude. In addition, several other design parameters such as the film length and bearing stiffness are discussed in the model sensitivity to demonstrate the significance of their impact.
Design of Viscoelastic Surfactant-oil-water Structures with the Hydrophilic-lipophilic Difference (HLD) and Net-average Curvature (NAC) Frameworks
Keywords: liquid crystals
micelles
microemulsion
rheology
surfactant

Manipulating the self-assembly of surfactants into viscoelastic structures such as wormlike micelles and liquid crystals is an important aspect in the development of personal care products and nanostructured materials. Central to this is the curvature of the surfactant membrane, which is one of the governing concepts of surfactant self-assembly. It can be altered with multiple parameters including differences in surfactant molecular structure, added salts, added oils, and temperature. Current frameworks used to guide the design of formulations such as the packing factor do not excel at predicting the necessary combination required to produce the desired structure. A new approach presented in this work relates the formation of viscoelastic structures including wormlike micelles and liquid crystals to curvature-related phase inversion phenomena observed in surfactant-oil-water systems. The phase inversion point, in turn, can be predicted with the hydrophilic-lipophilic difference (HLD) framework. This approach was successful at predicting the formation of viscoelastic fluids for extended anionic surfactants, and a model anionic surfactant, sodium dihexyl sulfosuccinate for a variety of salinities and polar/non-polar oils at low surfactant and oil contents (
Pharmacologic Inhibition of Ubiquitin Activation as a Novel Therapeutic Strategy in Acute Myeloid Leukemia
Keywords: ABCG2
AML
BEND3
TAK-243
UBA1
Ubiquitin

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy for which new therapeutic approaches are required. One such potential therapeutic strategy is to target ubiquitin-like modifier activating enzyme 1 (UBA1), the initiating enzyme in the ubiquitylation cascade in which proteins are tagged with ubiquitin moieties to regulate their degradation or function. Here, we evaluated TAK-243, a first-in-class UBA1 inhibitor, in preclinical models of AML and identified potential determinants of sensitivity to this drug. In AML cell lines and primary AML samples, TAK-243 induced cell death and inhibited clonogenic growth. In contrast, normal hematopoietic progenitor cells were more resistant. TAK-243 preferentially bound to UBA1 over the related enzymes UBA2, UBA3 and UBA6 in intact AML cells. Inhibition of UBA1 with TAK-243 decreased levels of ubiquitylated proteins, increased markers of proteotoxic stress and DNA damage stress. In vivo, TAK-243 reduced leukemic burden and targeted leukemic stem cells without evidence of toxicity. We selected populations of AML cells resistant to TAK-243 and identified missense mutations in the adenylation domain of UBA1. To identify the determinants of TAK-243 sensitivity, we conducted a genome-wide CRISPR/Cas9 knockout screen in AML cells in the presence of TAK-243. We identified BEN domain-containing protein 3 (BEND3), a transcriptional repressor and a regulator of chromatin organization, as the top gene whose knockout conferred resistance to TAK-243 in vitro and in vivo. BEND3 knockout dampened TAK-243 effects on ubiquitylation, proteotoxic stress and DNA damage response. It also upregulated the ABC efflux transporter breast cancer resistance protein (BCRP) resulting in increased efflux of TAK-243 out of the cells. In addition, TAK-243 sensitivity correlated with BCRP expression in cancer cell lines of different origin and chemical inhibition of BCRP sensitized intrinsically resistant high-BCRP cells to TAK-243. Thus, our data demonstrate that TAK-243 targets AML cells and stem cells and support a clinical trial of TAK-243 in this patient population. We also provide insights into potential mechanisms of acquired resistance to TAK-243. Moreover, our data demonstrate that BEND3 regulates the expression of BCRP for which TAK-243 is a substrate. Therefore, BCRP expression could serve as a predictor of TAK-243 sensitivity in different malignancies.
Reduced-order Modeling in the Finite-difference Time-Domain Method
Keywords: CFL limit
FDTD
model order reduction
stability analysis
subgridding

The finite-difference time-domain (FDTD) method is a well-known numerical algorithm. Despite its many advantages, FDTD becomes time-consuming when applied to multiscale problems, where sharp field variations or fine geometrical details impose a very fine grid, at least locally. Grid refinement affects computational cost in two ways: it increases the number of fields to update at each iteration, and it reduces the maximum timestep allowed by the Courant-Friedrichs-Lewy (CFL) stability limit. Our goal is to investigate how model order reduction (MOR) can be leveraged to address both computational issues associated with grid refinement, and devise accelerated FDTD schemes for multiscale problems. In the envisioned approach, multiscale objects are initially meshed with a locally-refined grid, while the rest of the domain is meshed with a coarse grid. Then, the FDTD update equations of each refined region are processed to generate a reduced-order model, which is finally coupled to the surrounding coarse grid. To achieve this vision, two main issues had to be addressed: i) how to generate FDTD-compatible reduced-order models, and ii) how to guarantee that the final FDTD scheme with embedded reduced models will be stable under a known CFL limit. Our first major contribution is to devise a new theoretical framework to create FDTD-like schemes with provable stability, based on the dissipativity theory. We show that most FDTD schemes can be seen as the connection of different subsystems, such as reduced-order models. We determine the conditions under which these FDTD-like subsystems are dissipative, and prove that, if each subsystem is dissipative, then the whole scheme will be dissipative, and thus stable. This theory provides a systematic way to create a variety of FDTD schemes with provable stability, from simple subgridding algorithms to the advanced FDTD schemes with embedded reduced-order models. Another major contribution is to generate reduced-order models compatible with FDTD simulations, and capable of accurately capturing the electromagnetic behaviour of a given volume enclosing arbitrary objects. The proposed models can be instantiated into a coarser FDTD grid and are compatible with leap-frogging. Through the dissipativity theory, we rigorously prove the stability of the proposed FDTD algorithms with reduced models.
Enhancing our Understanding of Outcomes and Determinants of Outcomes Following Proximal Humerus Fractures in Adults
Keywords: outcomes
predictors
Proximal humerus fractures

There remains significant debate surrounding the optimal management strategies for proximal humerus fracture (PHF) patients. High quality evidence summarizing and appraising the measurement properties and concepts reflected by outcomes used to evaluate recovery, and predictors of outcomes following PHF is needed. Objectives: To summarize and appraise 1) outcome measures; and 2) predictors of outcomes following PHF; and 3) develop novel risk tools to predict subsequent surgery following PHF. Methods: I performed four systematic reviews to discern 1) the measurement properties of outcomes; 2) identify the concepts reflected by these outcomes; and 3) summarize and appraise predictors of i) patient-reported functional disability, and ii) subsequent surgery following initialtreatment. I used these data to develop a population-based cohort of PHF patients, and novel risk tools to predict subsequent surgery following initial treatment. Results: The Disabilities of the Arm, Shoulder and Hand (DASH), Shoulder Function Index, and Euro-Quol-5D scores appear to have the best measurement properties to evaluate PHF patients.The DASH, American Shoulder and Elbow Surgeon’s, and Oxford Shoulder Scores appropriately address limitations in daily activities. While evidence surrounding predictors of outcomes was somewhat conflicting, there were trends toward worse outcomes in patients who were older (primarily in those treated with fixation), injured their dominant arm, and whosefracture had a varus fracture neck shaft angle, or a disrupted medial hinge. My risk tools identified the use of a bone graft, and fixation with a nail or wire (vs. a plate) in patients treated with fixation, poor bone quality in patients treated with replacement, and younger age, as well asdischarge to a destination other than home in patients treated non-surgically as predictors of subsequent surgery. The tools showed good to strong discriminative ability for patients treated with fixation and non-surgically. Conclusion: This thesis generated important new knowledge surrounding the outcomes and predictors of outcomes following PHF. My outcome studies can help clinicians choose measures for evaluating recovery, and for future research. My systematic reviews to identify predictors of outcomes can help select variables potentially associated with poor outcomes. My risk tools can identify patients at risk for subsequent surgery.
Morality Police: Sexuality Governance at the League of Nations
Keywords: Interwar Period
Magdalene Asylum
Moral Panic
Morality Police
Surveillance
Women's History

During the interwar period, the international community was zealously involved in the regulation of sexuality and vice under the auspices of the League of Nations. The roaring twenties had ushered with it a revival of morality policing in Europe and North America. The League of Nations Sex Trafficking Committee, led by social purity reformers and religious organizations, operated to create policy aimed at eliminating vice districts, music halls, and cabarets. Once this international policy was issued, volunteer organizations (spread literally around the globe) would carry out the carceral policy directives. Morality Police is the first genealogy of this remarkable period, providing an “ontology of ourselves” that seeks to expose the disreputable origins of anti-sex trafficking campaigns. This project narrates how the international community policed morality, following the twists and turns as they occurred on the Sex Trafficking Committee and at local levels from France to India. Drawing on over 10,000 archival documents collected from the League of Nations archive, this project argues that rather than being primarily concerned with abolishing state regulated prostitution, the Sex Trafficking Committee more insidiously engaged in a campaign of sexuality governance. While this campaign to halt changing sexual and cultural norms was ultimately unsuccessful, it was remarkably effective at repressing and disciplining sexual outlaws during its tenure. This project concludes with a stark reminder that while the campaign to stamp out vice and immorality in the interwar period was ultimately a failure, its legacy is still with us. Arguing that the laws and propaganda campaigns during this period created stories of international trafficking that were so powerful, the narratives became folklore that survived generations awaiting another eruption of moral panic.
Blossoming Multiliteracies: Stories of How W̱SÁNEĆ, Quw’utsun, Gitga’at, and Líl̓wat Nations Reclaim Indigenous Languages and Food Systems through Pedagogies of the Land
Keywords: Education
Ethnobotany
Indigenous
Land
Language
Reclamation

Indigenous languages are windows into a myriad of worldviews (Simpson, 2011). They are repositories of botanical, environmental, and kinship knowledges, and, perhaps more importantly, are central to Indigenous identity (McCarty et al., 2018). As W̱SÁNEĆ, Quw’utsun, Líl̓wat and Gitga’at communities (re)inhabit social, physical, spiritual, and emotional spaces to speak their languages of SENĆOŦEN, Hul’q’umi’num’, Ucwalmícwts, and Sm̓algya̱x, respectively, they use pedagogies of the land. Teaching styles are grounded in Indigenous land education (Calderon, 2014; Goodyear-Ka‘ōpua, 2013) and decolonizing botanical knowledges (Geniusz, 2009) as (w)holistic curricula, upholding ontologies of lands and waters. As a settler researcher on these lands, I engaged in conversations with nine Elders and educators from Coast Salish (SȾÁUTW̱, W̱JOȽEȽP, W̱SÍKEM, Quw’utsun), Gitga’at, and Líl̓wat First Nations, and two settlers. Research questions inquired into how youth and Elders approach language reclamation. I learned pedagogies of the land are a return to ancestral ways of being, counter-hegemonic actions that pull children and adults towards nature-based spaces, nurturing whole beings. Conceptual frameworks integrate anti-colonial (Carlson, 2016), Indigenous-centred methodologies (Smith, 2012). Conscious of “unsettling” (Regan, 2010) my positionality as active witness (Atkinson, 2001), I gathered knowledges through conversational interviews (Kovach, 2010) and storywork (Anderson, 2011; Archibald, 2008), contributing through eco-cultural restoration. Knowledge Keepers shared stories of teaching on the land, drawn to sacred places through keystone food systems, interweaving Oral Histories with Indigenous languages. Stories are linked thematically through an iterative framework, and shed light into how Indigenous languages are transmitted intergenerationally, grounded in local epistemologies. Findings show how first (L1) and second (L2) language acquisition connects with ethnobotanical knowledges; blending mariculture, prayer names, traditional practices, and songs. Foods and medicines are harvested in reciprocal acts of gratitude. Through this work, multiple layered literacies develop, with students learning and speaking Indigenous languages through (w)holistic, land-centred education (heart- and community-literacies), while regenerating lands, waters, and medicines (food- and ecological-literacies). Languages grow as part of linguistic ecologies (Twitchell, 2017), thriving within the seen and unseen, more than human world. This thesis may interest those in the fields of language revitalization; food sovereignty, security, and native plants; language policy; eco-justice; and land-based Indigenous pedagogies.
Electrochemical Study of Proteins using Electrode with Modified Surfaces
Keywords: Bilayer
Diazonium salt
Electrochemistry
Hemoglobin
Impedance Spectroscopy
Protein

Some different aspects of proteins properties as well as nanostructures were studied using various electrochemical approaches in this thesis. Electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), differential pulse voltammetry (DPV) were employed as well as many other analytical tools and methods to explore some structures of our interest. In the first chapter, the above-mentioned electrochemical methods along with some fundamental background of electrochemistry were reviewed. The chapter, also, reviews some aspects of membrane proteins, membrane double layers and chemistry of diazonium compounds which were employed in our studies. The structure of a novel (and patented) nanostructure and mainly its response to electrochemical impedance spectroscopy was studied and discussed in chapter 2. We showed how we can isolate the response of this nanosensor to a small change of the dielectric constant of the material entraps in the nanogap of the sensor. In chapter 3, we used DPV and CV methods to investigate nitrite reduction activity of human hemoglobin. We proposed -for the first time- a complete reaction mechanism for the electrochemical reactions taking place on the surface of modified glassy carbon electrodes. We showed how these electrochemical results were comparable to spectroscopic methods and can be used for future studies of hemoglobin nitrite reduction studies. In chapter 4, we developed a novel platform for preparing a hybrid bilayer (HBM) for electrochemical studies of membrane proteins. We used diazonium chemistry to graft the first layer of the HBM covalently to the glassy carbon electrode. We demonstrated the flexibility of our platform for developing various bilayers with relatively predictable characteristics using molecules with desired properties as the first and second layer in HBM. We used two different electrochemical probes with opposite charges to show how differently the HBM responded to these probes depending of the charge of the polar groups on the second layer. We used amyloid-β42 to demonstrate the application of this platform to study protein aggregation processes. In chapter 5, we discussed some future directions for all previously discussed chapters and mentioned some potential studies which may follow these studies.