21793 research outputs found
Sort by
Functional analysis of metabolic circuits and drug response in Candida albicans
Get PDFCandida albicans, an opportunistic pathogenic fungus, is a leading cause of nosocomial infections. In last two decades, the rise of antifungal resistance calls for better understanding of genetic networks responsible for mechanisms of resistance. Genetic analyses have been fundamental in unveiling cell adaptation mechanisms and transcriptional rewiring. High-throughput data from the Gene Replacement and Conditional Expression 1.0 collection of gene inactivations identified strains resistant to the common antifungal fluconazole, including RAP1, ERG3 and HCS1. Using CRISPR-Cas9, we generated targeted single and double deletion mutants of these genes and studied their response to fluconazole treatment. Our study reveals functional diversity in strains lacking RAP1. RAP1 deficiency also causes colony size heterogeneity and morphological changes to pseudohyphae. We also utilized an activated transcription factor library to perform a high-throughput screenings with different stressors including pH, heavy metal tolerance, and fluconazole. We were able to find interesting phenotypic responses such as four TFs whose activation conferred resistance to hydroxyurea, eight involved in pH response and six in temperature response. Moreover, one strain with transcription factor Adr1 activated showed multidrug resistance, and we identified a change in function rewiring from control of ergosterol biosynthesis in Candida albicans to control of alcohol and fatty acid metabolism in Saccharmocyes cerevisiae. Our findings thus highlight two genes with involvement in fluconazole response which can provide new insight to the transcriptional regulation of C. albicans and potentially direct more effective treatments
Navigating Museum Education Beyond Objects: Collaborative Pedagogies and Emerging Tech
Get PDFIn the past decade, particularly accelerated by the COVID-19 pandemic, cultural institutions and museums have significantly enhanced their digital offerings and experiences. These new virtual spaces serve purposes beyond conveying information to visitors and enticing them to visit the physical museum; they provide innovative teaching and learning contexts that necessitate the development of new pedagogical approaches. This manuscript-based thesis draws on participatory and collaborative practices to conduct an educational design-based study at the Oxford Natural History Museum. The initial manuscript delineates the evolution of theories pertaining to museum education, transitioning from traditional object-centered paradigms to those centered on the visitor. Subsequently, I expand this continuum to articulate a novel framework for a post-object and post-visitor museum education. The second manuscript is methodological. The emergence of new learning digital contexts calls for new methodologies to analyze them. Through a case study, the article focuses on developing a coding rubric to analyze two virtual reality museum experiences: Mona Lisa: Beyond the Glass by the Louvre and Curious Alice by the Victoria and Albert Museum. The third and final manuscript examines the collaboration among educators, communications specialists, and young visitors aged 15 to 24 at the Oxford Natural History Museum in creating educational social media content. I connected the manuscripts through two bridges, where I conversed with different museum chatbots powered by artificial intelligence. Through these conversations, I reflect on how these chatbots blur the boundaries between the physical objects in museums and their digital representations or imaginaries, as well as the implications of this evolution for museum education. I conclude with thoughts on the influence of this research and its implications for forthcoming studies. This thesis contributes to the insufficient research concerning museum learning within digital environments and it also makes a meaningful contribution to the growing body of literature regarding the function of museums in the digital ecosystem
Innovative In Vitro Model to Replicate Uterine Fibroid Ablations with Cryotherapy
No full textUterine fibroids significantly impact patients’ quality of life, often causing severe pain and other debilitating symptoms. Treatment options are limited, with hysterectomy being the most common, despite its long recovery time, loss of fertility, and potential early menopause. Alternative treatments exist but none have not become the standard of care and each have their own downsides. This study explores the feasibility of using cryotherapy for fibroid ablation and focuses on developing a catheter and an experimental, in vitro, model for testing.
A cryoablation catheter was designed based on commercially available cardiac ablation catheters, with modifications to increase the tip’s surface area. The catheter was optimized to maintain temperatures close to −89°C while avoiding ice blockages that could halt the procedure. Testing was conducted on three different tissue models, each designed to mimic real fibroid tissue, to determine which posed the greatest challenge for ablation. Tissue A, the densest, was identified as the most difficult to ablate and so was selected for further modeling.
The study demonstrated that the catheter could effectively ablate fibroids up to 5mm in size, reaching through the uterine wall thickness and treating fibroids in various locations. While a single ablation was insufficient to fully treat an average-sized fibroid, multiple ablations could enable treatment of submucosal and subserosal fibroids, offering a safer alternative to patients who want to keep their reproductive organs. Future work will explore further catheter modifications to treat intramural fibroids, either by increasing the ablation surface area or by ablating from the inside out, reducing the risk to surrounding tissues compared to heat-based ablation methods. Further development of the tissue model could enhance its accuracy and versatility for testing
Convergences in Twentieth-Century Radical Environmentalisms: Environmental Justice and An Ecological Perspective In the Works of Rachel Carson, Murray Bookchin, Arne Naess, and Carolyn Merchant
Get PDFThis essay analyzes the works of four authors who began writing in the field of radical environmentalism in the second half of the twentieth century: Rachel Carson, Murray Bookchin, Arne Naess, and Carolyn Merchant. An examination of the works of each author illustrates the convergences that exist between the disparate forms of radical environmentalism for which they call. They share an ecological perspective, a focus on environmental justice, the values of unity and diversity, and the goal of synthesizing social justice movements through a change in popular consciousness. This essay demonstrates the continued significance of these shared values as the effects of anthropogenic climate change continue to escalate and concludes that the ecological perspective’s focus on relationality is even more relevant in today’s increasingly interdependent, globalized world
Nonreciprocal Vibration Transmission in Nonlinear Mechanical Systems: Energy-Preserving, Phase-Preserving and Unilateral Transmission
Get PDFReciprocity, a fundamental property of linear, time-invariant systems, implies that wave transmission characteristics between two points in a material or structure remain unchanged upon interchanging the locations of the source and receiver. Thus, reciprocal systems cannot have direction-dependent transmission properties. One way to overcome this limitation is to utilize nonlinearity.
There has been a surge of interest in the past two decades in nonlinear nonreciprocity in the context of phononic crystals, metamaterials and lattice materials. This thesis contributes to this body of knowledge by providing a detailed account of three nonreciprocal transmission regimes: energy-preserving, phase-preserving and unilateral transmission. This computational investigation is focused exclusively on the steady-state response of spatially periodic systems to external harmonic excitation.
The most salient indicator of nonreciprocity is the ability of a system to support unidirectional transmission. This occurs when there is a large difference between the energies transmitted in opposite directions. This energy bias is accompanied by a difference in the phase of the transmitted vibrations. The role of the phase bias in nonreciprocity has primarily been overlooked in the literature. To highlight the role of phase, we consider two limiting cases. We demonstrate the existence of response regimes in which the energy bias is zero and nonreciprocity is solely caused by the phase bias. Moreover, we show that energy bias alone, without any contribution from phase, can still lead to nonreciprocity, but only at very finely tuned system parameters. We provide methodologies for systematically realizing response regimes of energy-preserving and phase-preserving nonreciprocity.
Furthermore, we investigate unilateral transmission, a phenomenon in which transmitted vibrations remain purely in tension or compression. We investigate unilateral transmission in a system with different effective elasticity in compression and tension. We show that breaking the mirror symmetry of the system in either the elastic or inertial properties enables unilateral transmission to occur near the primary resonances.
This dissertation advances the understanding of nonlinear nonreciprocity in vibration systems, with a focus on three response regimes that are characterized by distinct dynamic features. These findings provide new insights into the design of nonlinear waveguides and mechanical systems with tunable nonreciprocal properties
Enabling Cellular Network Power Infrastructure to Provide Frequency Regulation Services
No full textOver the past decades, the management and operation of power grids have undergone significant changes, posing numerous challenges for utility companies. With growing societal concerns about the environment, there has been a rapid increase in the penetration of renewable energy sources. Because renewable energy sources (such as wind turbines and solar panels) are inherently intermittent, their integration into the power grid can result in undesirable fluctuations in the power system due to potential imbalances between energy production and consumption.
Ancillary services have been introduced to serve as mechanisms to support the continuous flow of electricity, ensuring that demand and production are met in real-time. Given the rapid response capabilities of batteries, their owners are encouraged to participate in bids for one of the most crucial ancillary services: Frequency Containment Reserve (FCR). Through this participation, they can generate new revenue opportunities and contribute to the stability of the electricity grid.
In this thesis, we explore mathematical models and heuristics for the planning and coordination of cellular network systems aiming to provide FCR-D ancillary services. By exploiting the spare battery capacity associated with their multiple cellular base stations, communications service providers (CSPs) emerge as a potential players in this market. We compare different mathematical models and heuristics applied to the Swedish frequency market, considering a large CSP with one thousand cellular base stations. The results demonstrate the effectiveness of the proposed models in terms of transparency of participation, profit and associated costs. Furthermore, we validate the technical and economic feasibility of frequency regulation provided by cellular network systems, thus revealing a potential new source of revenue for CSPs
Design, Structure-Activity-Relationship Study and Synthesis of 1,3,5-Triazine Derivatives as Candidates for Positive Allosteric Modulators of GPR68
No full textG-protein-coupled receptors (GPCR) are the largest family of proteins encoded in
the genome, which transduce signals for the most diverse ligands of any receptor
family. GPR68, a transmembrane receptor that can induce physiological effects when
activated by protons, belongs to this class and its considered a promising target for the
treatment of ischemia, as its Gq subunit is involved in the release of calcium, which may
promote stem cell differentiation and make GPR-68 an attractive target for anti-ischemic
candidates. Ogerin, a small molecule containing a triazine core, it’s the only well known
GPR68 ligand, and revealed neuroprotective effects as stimulate Gq subunit, being
considered a lead compound for the design of potential candidates. Thus, through the
use of several drug design strategies and applying Structure-Based Drug Design
(SBDD) approach, four structural classes of triazine derivatives were synthesized,
biologically tested and computationally docked, aiming to continue Structure-Activity
Relationship (SAR) studies. Although the employed synthetic methodologies proved to
be efficient, allowing the obtention of 37 compounds, only three of them could slightly
stimulate GPR68-Gq. Thus, based on the real biological data, combined with the
molecular docking results, it’s first possible to propose that the triazine motif acts as the
pharmacophore, due to its strong HBA tertiary nitrogen group, which can effectively
interact with GPR68. On the other hand, the replacement of a HBD (hydrogen from
amine) group by a HBA (methoxy) at the position 4 of the triazine ring eliminates the
activity, while the replacement of a HBD (hydrogen from hydroxymethyl) by a strong
HBA (cyano) at the ortho position of the phenyl ring increased it. The addition of
fluorines and heterocycles, as well as the removal of the single bond in the benzylamine
ring, didn’t contribute to the potency as well. These findings will help in guiding the
development of the next generation of Ogerin’s derivatives, asses their GPR68-Gq
stimulation, and advance SAR studies, to obtain promising active molecules
Do L2 Speakers’ Assumptions About the Test Examiner Influence Their Speaking Anxiety in an Oral Exam? A Reverse Linguistic Stereotyping Study
No full textA speech may be perceived differently depending on what social information we draw from the speaker, be it correct or misguided (Burgers & Beukeboom, 2020; Edwards, 1999; Lambert et al., 1960; Niedzielski, 1999). The phenomenon where non-linguistic social information about the speaker (e.g., race, occupation, etc.) influences our actual experience with speech is called reverse linguistic stereotyping (RLS; Kang & Rubin, 2009). Although RLS has been well documented for its influence on speech perception (e.g., seeing an Asian face can render a speech less comprehensible and more accented), its broader impact on speakers is still less known. This study, therefore, examined how L2 speakers’ assumptions about examiners influence their speaking anxiety in an oral exam.
Participants included 40 Mandarin-speaking international students in Montreal, who completed two English speaking tests delivered through video prompts. Each test featured a different examiner (Caucasian or South Asian), while the audio remained constant (Canadian English). Participants rated their speaking anxiety before and after each test and evaluated each examiner. Retrospective recall interviews were conducted with eight individuals who showed noticeable difference in pretest anxiety ratings across two examiners. Results revealed no significant difference in speaking anxiety in Test 1. However, a higher pretest anxiety was observed in Test 2 when the examiner appeared South Asian than Caucasian, possibly due to a shift in visual stimuli, which activated the stereotypical association between examiner’s race and linguistic ability. The findings highlighted the importance of creating a more inclusive environment in both language learning and assessment
Mixing Dynamics in Yield Stress Fluids
No full textMixing is a common process in many natural and industrial applications, such as food processing, pharmaceuticals, oil extraction, and more. Despite its ubiquity, mixing remains one of the most challenging paradigms in engineering to define, analyze, and understand systematically. In many of these applications, the working fluid exhibits a yield stress behavior.
Traditionally, mixing has been extensively studied under the assumption of homogeneity, i.e., the influence of heterogeneous fluid properties on the development of mixing is neglected. Therefore, empirical relationships are often used to estimate the mixing time and energy consumption. However, heterogeneity can play a crucial role in mixing dynamics, which is not captured by the current empirical relationships. Moreover, the effect of yield stress on mixing has often been examined qualitatively, with studies typically reporting that yield stress leads to mixing localization. Despite these observations, a mechanistic framework to describe the relationship between flow dynamics and mixing development in yield stress fluids remains lacking. In this thesis, we study the flow dynamics and mixing development in yield stress fluids.
To demonstrate the potential impact of heterogeneity on mixing dynamics and efficiency, we explore the homogenization of an additive in a cylindrical tank stirred by a disk. Two cases are considered: in the first (model problem T), both the fluid rheology and density depend on an additive concentration; in the second (model problem M), the additive is passive, meaning that the fluid rheology and density remain independent of the additive. We specifically examine the impact of neglecting buoyancy on mixing and flow dynamics. Our results show that, in model problem T, the mixing rate increases significantly in the presence of small buoyancy forces compared to model problem M. However, as buoyancy becomes large, the mixing rate decreases.
To establish a mechanistic framework linking fluid dynamics and mixing development, we develop a simplified model problem consisting of an infinite two-dimensional domain where a cylindrical stirrer moves along a circular path. First, we analyze the flow dynamics and mixing behavior for a Newtonian fluid at various stirring rates to identify different mixing mechanisms in the absence of a yield stress. We propose four distinct flow regimes based on the flow and mixing development at different stirring rates: (i) no shedding, (ii) weak shedding, (iii) trapped vortices, and (iv) escaped vortices. We further show that mixing is independent of the stirring speed when mixing is confined near the stirrer.
Finally, we explore stirring a Bingham fluid in the same setup to characterize the influence of yield stress and localization mechanisms. We demonstrate that introducing yield stress leads to mixing localization through three distinct mechanisms: (i) escaped shedding, (ii) trapped shedding, and (iii) suppressed shedding. We propose a classification of mixing regimes based on the identified localization mechanisms. We show that these regimes can be distinguished using spectral analysis of kinetic energy oscillations, revealing critical transition criteria
The Evolution of the Catholic Church's Presence in Quebec: From Priests from France to Priests from Africa
No full textThe Evolution of the Catholic Church's Presence in Quebec: From Priests from France to Priests from Africa
Evans Masakhalia
Until its secularization, Quebec was characterized by cultural Catholicism that penetrated all its social structures. After the 1960s Quiet Revolution, which is considered the beginning of secularization of Quebec, there has been a noticeable abandonment of the institutional Church. This has led to a decline in the priestly vocations. The Catholic bishops of the Quebec Church, which once flourished with vocations, have been compelled to invite priests from elsewhere to serve in their dioceses. The Quebecers’ memory of their triumphal Church before secularization continues to lead to varying hypotheses. This thesis attempts to study the evolution of Catholicism in Quebec, its adaptation to secularization and the relevance of priests from elsewhere, taking African priests as a case study