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Characterization of Emodepside’s interaction with SLO-1 Potassium channels in Filarial parasites
No full textABSTRACT
Filarial parasites cause debilitating health problems and remain difficult to control and manage. Amongst them, Onchocerca volvulus, which causes onchocerciasis (river blindness) and Brugia malayi, which causes lymphatic filariasis, are the most significant due to their widespread impact and potential for severe disability. Therapeutic options are limited, and no effective vaccine exists. Current treatment primarily relies on mass drug administration with ivermectin, which only kills microfilariae and is not effective in eliminating the adult worms. Additionally, concerns have been raised about the potential development of ivermectin resistance due to prolonged or improper use. Therefore, there is a critical need to develop more effective treatment options. Given the high cost and lengthy timelines associated with traditional drug discovery and development, drug repurposing has emerged as an attractive alternative for identifying new therapies. As such, emodepside, a broad spectrum anthelmintic used in veterinary medicine has garnered attention for its potential efficacy against all stages of the filarial worms. While emodepside’s potency is attributed to its ability to activate the calcium activated and voltage sensitive potassium channels (SLO-1K), its molecular mechanism of action has not been fully characterized. Hence this dissertation aims to contribute knowledge to help bridge that gap.
First, we provide an overview of onchocerciasis, discussing its pathogenesis, clinical spectrum and advances in drug development along with the associated challenges. Subsequently, we present a mini review on the mode of action and toxicity of emodepside, synthesizing existing literature to provide insights into its spectrum of activity, mode of action, pharmacokinetics, efficacy and potential toxicity.
Next, we expressed SLO-1K isoforms from O. volvulus (Ovo-SLO-1A) and B. malayi (Bma-SLO-1F) in Xenopus oocytes and evaluated emodepside’s effect on these channels using the two-electrode voltage clamp (TEVC) electrophysiology technique. We demonstrated that Ovo-SLO-1A is more sensitive to emodepside than Bma-SLO-1A and highlighted specific regions that may explain this sensitivity difference. Additionally, we showed that GoSlo-SR-5-69, a mammalian BK (Big Potassium) channel opener, has no effect alone but enhances the effect of emodepside on both channel isoforms. Thus, our findings highlight the pharmacological similarities and differences between the two filarial nematode SLO-1K channel isoforms. They also reveal the allosteric modulation of these channels by a mammalian BK channel activator, providing evidence that supports strategies to increase emodepside potency.
Finally, we expressed the Ovo-SLO-1A isoform in HEK 293 cells and used patch clamp electrophysiology to investigate the channel’s behavior in the presence and absence of emodepside. Our findings revealed that, under control conditions, the channel exhibited flickering activity, opening to at least three equally spaced sub-conductance levels in addition to the main state. Emodepside increased open rates and decreased close rates, increased mean current amplitude, burst-times and open probability (Popen). Verruculogen, a BK channel inhibitor, inhibited channel activity both in the presence and absence of emodepside. Hence, we highlight emodepside’s key molecular modulatory mechanisms relevant to filarial drug targeting.
Overall, this dissertation advances our understanding of how emodepside interacts with SLO-1K channels at the molecular level and emphasizes its promise as a potential antifilarial drug. The findings presented here open new avenues for developing more effective therapies and addressing drug resistance in filarial infections
Development and testing of a DRAINMOD-based decision-support tool for designing and evaluating saturated buffers
No full textSaturated buffers (SBs) are an effective edge-of-field practice for reducing nitrate loads from agricultural drainage, contributing to improved environmental water quality. However, no software currently exists to design SBs based on site-specific conditions or to quantify their environmental benefits. The objective was to develop and test a DRAINMOD-based tool for predicting drainage discharge and nitrate load removal (NLRSB) under local weather, soil, field drainage, and SB characteristics. We present SBTool, a novel decision-support tool that integrates the DRAINMOD hydrologic model with a nitrate-removal module to simulate SB performance. SBTool was validated using field data from two Iowa sites (2014–2022). Model predictions for discharge (QDD), diverted flow (QDP), and NLRSB showed good agreement with observed data. Prediction errors of QDP and NLRSB were only 5.7 % and 6.1 %, respectively, at the eight-year site, and −17.5 % and −13.6 % at the four-year site. Unlike existing design methods, SBTool enables site-specific evaluation and design of SBs, supporting conservation planning and nutrient trading through credible, field-based quantification of nitrate removal.This article is published as Abdalaal, Yousef, Ehsan Ghane, Josué Kpodo, A. Pouyan Nejadhashemi, Mohamed A. Youssef, Anamelechi Falasy, Manal Askar et al. "Development and testing of a DRAINMOD-based decision-support tool for designing and evaluating saturated buffers." Agricultural Water Management 326 (2026): 110201. https://doi.org/10.1016/j.agwat.2026.110201This work was partly funded by the Michigan Department of Agricultural and Rural Development (791N7700580) and the Classic Conservation Innovation Grant (USDA-NRCS-NHQ-CIG-20-GEN0010808) from the US Department of Agriculture's Natural Resource Conservation Service
Processing-microstructure-property relationships in additively manufactured duplex stainless steels
No full textMetal additive manufacturing (AM) has seen rapid expansion in the last decades. One family of alloys that are becoming more popular in AM applications are duplex stainless steels (DSS), known for their excellent mechanical and corrosion properties. These alloys are commonly used in the oil and gas, chemical, and marine industries. However, since AM can drastically change the properties and microstructure of materials compared to traditional methods, the processing-microstructure-property relationships of AM DSS materials are not fully understood.
To address this knowledge gap, this work investigates the influence of processing parameters in laser powder directed energy deposition (LP-DED) and wire arc additively manufactured (WAAM) DSS alloys. A series of LP-DED samples at varying laser powers and scanning speeds were characterized to elucidate the complex influence processing parameters have on the microstructure and properties, specifically the defect content, phase fraction, and microindentation hardness.
Various scanning strategies including raster, zigzag, spiral, and a serpentine pattern were investigated to understand their influence on the microstructure of AM DSS materials, specifically the grain size, grain shape, and texture.
To boost the speed and efficiency of the characterization of processing-microstructure-property relationships for DSS alloys, thermomechanical simulations to simulate AM thermal histories using Joule heating were performed and the thermal histories were validated with a finite element analysis (FEA) model. The various thermal histories that were seen during these simulations lead to a wide variety of microstructures and properties with which preliminary microstructure-property relationships were obtained, showing that the phase boundary area density is an important feature that determines the mechanical properties.
To expand upon the versatility of quick thermomechanical simulations, thermomechanical simulations were used as a ‘proxy’ dataset to expand on an important ‘reference’ dataset. A relatively large dataset from the thermomechanical simulations on cheap wrought materials was used to bolster a more expensive and relatively smaller dataset from a WAAM build. Using machine learning with both the ‘proxy’ and ‘reference’ dataset, interpretable microstructure-property relationships were attained, showing that 65% of the mechanical properties are determined by the intrinsic strength (internal friction stress, solid solution strengthening, and dislocation strengthening) while the rest of the mechanical properties are determined by the microstructure with 20% coming from the phase fraction and 15% coming from the microstructure refinement.
To show a full breadth of experiments, a case study on the deposition of WAAM DSS is included. This study shows the prevalence of residual stress in large-scale AM and the importance of and process optimization while showing the potential for a low-nickel wire feedstock replacement for normal DSS wire feedstocks. This research shows the challenges that are inherent to large-scale AM and some of the methods executed to circumvent these challenges
Rotating Synchrotron Radiation (RoSyRa): photon emission from magnetized and rotating quark-gluon plasma
No full textThis paper investigates the production of non-prompt photons originating from rotating synchrotron radiation (RoSyRa), specifically the emission of photons by a rigidly rotating quark-gluon plasma in thermal equilibrium, in the presence of an external magnetic field. We compute the non-prompt photon spectrum and its elliptic flow (v2) at mid-rapidity. In particular, we investigate the finite volume effects. We find that at low transverse momentum, the magnetic field induces a significant v2, while the plasma rotation boosts the synchrotron radiation of negatively charged quarks. These effects account for both the observed excess of direct photons and their elliptic flow, contributing to the resolution of the "direct photon puzzle".This is a preprint from Buzzegoli, Matteo, Sergiu Busuioc, Jonathan D. Kroth, Nandagopal Vijayakumar, and Kirill Tuchin. "Rotating Synchrotron Radiation (RoSyRa): photon emission from magnetized and rotating quark-gluon plasma." arXiv preprint arXiv:2602.13044 (2026). doi: https://doi.org/10.48550/arXiv.2602.13044.The work of M.B. and S.B. was supported by the European Union - NextGenerationEU through grant No. 760079/23.05.2023, funded by the Romanian Ministry of Research, Innovation and Digitization through Romania’s National Recovery and Resilience Plan, call no. PNRR-III-C9-2022-I8. The work of K.T., J.D.K., and N.V. was supported in part by the U.S. Department of Energy under Grant No. DE-SC0023692
Kinetic-based techno-economic and life cycle assessment of slaughterhouse waste co-digestion for renewable natural gas production
No full textThere is a critical need for research into clean alternative energy sources to address future energy requirements. Renewable natural gas (RNG) can play a key role in sustainably meeting the projected increasing demand for natural gas. This study presents a techno-economic analysis (TEA) and life cycle assessment (LCA) of the anaerobic co-digestion of slaughterhouse waste (SW), domestic waste (DW), and bovine manure (BM). A kinetic model based on experimental data was developed and integrated into BioSTEAM, providing a robust evaluation of process performance and feasibility. The proposed process achieved higher biogas yields and produced biochar as a valuable co-product, contributing to a reduction in the minimum selling price (MSP) of RNG. The
plant is projected to generate approximately 172 GJ⋅year−1 RNG, with an estimated MSP of 2.1 $ kg−1 RNG. The global warming potential (GWP) was calculated at −4.73 kg CO2−eq kg−1 RNG, highlighting the environmental benefits of co-digestion and the carbon sequestration potential of biochar. Sensitivity analysis identified residence time and the inoculum-to-substrate ratio (ISR) as the main factors influencing MSP and emissions, respectively. This integrated framework, combining experimental kinetic data, process modeling, TEA, and LCA, demonstrates the technical, economic, and environmental feasibility of waste-based RNG production systems, offering insights into circular bioeconomy strategies for sustainable energy and carbon management.This article is published as Lorenzo, David, Aria Abbaspour, Yasmine Ryma Ouahabi, and Mark Mba Wright. "Kinetic-based techno-economic and life cycle assessment of slaughterhouse waste co-digestion for renewable natural gas production." Chemical Engineering Journal (2026): 173365. doi: https://doi.org/10.1016/j.cej.2026.173365
Reconstructing dynamic correlation and bonding in curved pi-systems
No full textThe first chapter of this dissertation presents the theoretical framework that underpins modern electronic structure theory. The next two chapters, 2 and 3, apply the QUAOs bonding analysis to interpret π-localization in curved and compositionally mixed rings. These chapters formalize the quasi-atomic orbital (QUAO) analysis used throughout the applications, including occupancies, hybridizations, and both bond order (BO) and kinetic bond order (KBO) metrics, and demonstrates the method on canonical π-systems to establish reference behavior. Chapter 3 further applies this framework to belt-shaped, alternately substituted Si/C annulenes across multiple ring sizes, integrating magnetic criteria and reaction-path analysis. The study reveals how curvature and 3p/2p orbital mismatch limit π-delocalization without invoking classical bond-length alternation, and contrasts these trends with the all-carbon analogue.
Chapter 4 broadens the methodological thread by combining spin-flip ORMAS wave functions with on-top pair-density functionals (MC-PDFT). It introduces a valence-virtual-orbital truncation that preserves accuracy while reducing cost. It benchmarks the approach on representative excitation and torsion problems to situate it alongside RI-ZAPT2 in the toolbox for dynamic correlation. Chapter 5 concludes the dissertation by synthesizing the algorithmic and conceptual advances, highlighting how representation: low-rank factorization on the methods side and localized chemically intuitive orbitals on the analysis side, enables both scalable computation and clearer interpretation, and by outlining opportunities for GPU kernels
Enhancing L2 Learners’ Perceived Social Presence and Vocabulary Learning Grit: The Mobile Vocabulary Learning-Pal Gamification
No full textVocabulary learning has been a challenge for second language (L2) learners, often due to its repetitive nature and the massive time investment it requires. To address these challenges, digital gamification features have been introduced to L2 learners and educators in higher education contexts to enhance the learning experience and foster learner grit. This study examined the impact of a mobile collaborative gamification feature, the learning-pal activity, on L2 vocabulary acquisition, focusing on learners’ vocabulary learning grit and perceived social presence. Using a quasi-experimental design, 100 L2 students from a Chinese university were divided into two groups: an experimental group (N = 62), which used the learning-pal feature within the Shanbay Danci (SBDC) app, and a control group (N = 38), which used the app without the collaborative feature. Employing a mixed-methods approach, the study found that participation in the learning-pal activity significantly improved learners’ vocabulary learning grit. However, the activity did not significantly enhance perceived social presence; notably, the experimental group reported lower levels of perceived social presence than the control group. These findings suggest that mobile collaborative gamification can effectively foster sustained vocabulary learning efforts but provide limited opportunities for social interaction during the vocabulary learning process.This article is published as Xu, Q.; Zhang, Z.; Richardson, J.C. Enhancing L2 Learners’ Perceived Social Presence and Vocabulary Learning Grit: The Mobile Vocabulary Learning-Pal Gamification. Educ. Sci. 2026, 16, 278. https://doi.org/10.3390/educsci1602027
Analog circuit sizing via lookup table-driven surrogate-assisted global optimization
No full textThis thesis presents a fast and reliable analog circuit sizing framework that combines gm/ID lookup table
modeling with a Surrogate-Assisted Differential Evolution algorithm. Transistor performance is estimated
directly from pre-characterized LUTs, eliminating the need for repeated SPICE simulations. An Artificial
Neural Network surrogate predicts how circuit specifications change with design parameters, and is
periodically updated using LUT data to maintain accuracy. A spec-aware cost function helps balance
performance trade-offs. Tested on a two-stage Miller OTA in a 180 nm CMOS process, the proposed
method significantly reduces optimization time while still meeting all required specifications,
demonstrating its practicality for data-driven analog design automation
A systematic exploration of configuration failures in flight control software
No full textSmall uncrewed aerial systems (sUAS) are growing in their use for commercial, scientific, recreational, and emergency management purposes. A critical part of a successful flight is a correctly tuned controller which manages the physics of the vehicle. If improperly configured, it can lead to flight instability, deviation, or crashes. These types of misconfigurations are often within the valid ranges specified in the documentation; hence, they are hard to identify. Recent research has used fuzzing or explored only a small part of the parameter space, providing little understanding of the configuration landscape itself. In this work we leverage software product line engineering to model a subset of the parameter space of a widely used flight control software, using it to guide a systematic exploration of the controller space. Via simulation, we test over 20,000 configurations from a feature model with 50 features and 8.88x10^34 products, covering all single parameter value changes and all pairs of changes from their default values. Our results show that only a small number of single configuration changes fail (15%), however nearly 40% fail when we evaluate changes to two parameters at a time. We explore the interactions between parameters in more detail, finding what appear to be many dependencies and interactions between parameters which are not well documented. We then explore a smaller, exhaustive product line model, with eight of the most important features (and 6,561 configurations) and uncover a complex set of interactions; over 48% of all configurations fail
An Innovative Ventilation and Cooling Strategy Based on the Thermal Comfort of Growing-Finishing Pigs
No full textDuring the growing-finishing phase of pig production, mitigating heat stress is essential to maximize growth performance, improve feed efficiency, and minimize risks of deteriorating animal welfare and farm profitability. Housed Swine Heat Stress Index (HS2I) assesses pigs‘ thermal comfort into a dimensionless metric scored from 0 (no heat stress) to 10 (severe heat stress), where 3 marks the beginning of heat stress along the range. Focusing on thermal comfort, a ventilation and cooling strategy based on the HS2I was implemented through precise control of air velocity and cooling using water sprinklers. The objective of this study was to optimize this strategy by adjusting two main parameters: the HS2I setpoints (2.0, 2.5, or 3.0) and the water sprinkling volumes (partial, gradual, or complete). Experiments were conducted in laboratory rooms housing 14 pigs under simulated summer-like conditions to test nine functional treatments of the strategy. The results showed that reduced water use through partial sprinkling was generally adequate to maintain pig performance, regardless of the selected HS2I setpoint. However, the combination of an HS2I setpoint of 3.0 with a reduced sprinkling strategy may expose heavier pigs (>100 kg) to heat stress. These findings offer practical insights for optimizing cooling strategies in pig production systems that face heat stress challenges.This article is published as Quirion, Rémi, Jean-Gabriel Turgeon, A. Dalila Larios-Martinez, Azin Zand Miralvand, Alexis Ruiz-Gonzalez, A. Katherín Carranza-Diaz, Sébastien Turcotte et al. "An Innovative Ventilation and Cooling Strategy Based on the Thermal Comfort of Growing-Finishing Pigs." Applied Engineering in Agriculture 42, no. 1 (2026): 13-28.
doi: https://doi.org/10.13031/aea.16458.This study was funded by the Programme Innov’action agroalimentaire (IA121707), a program from the Canada- Quebec agreement for the implementation of the Canadian Agriculture Partnership between the Ministère de l’Agriculture, des Pêches et de l’Alimentation du Québec (MAPAQ) and Agriculture and Agri-Food Canada (AAFC). Funding was also provided by the Mitacs Acceleration Program (IT31892) and the Centre de recherche en infectiologie porcine et avicole (CRIPA; https://doi.org/10.69777/309365)