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Ubisol-Q10 Treatment Prevents Substantial Memory Loss and Reduces β-Amyloid Plaques in a Transgenic Mouse Model of Alzheimer's Disease
No full textThere is currently no cure for Alzheimer's disease (AD), a progressive, neurodegenerative disease that causes severe memory deficits and personal hardship. Animal models are useful for studying the progression of AD as neurodegeneration begins in the region of the brain called the hippocampus, which leads to changes in specific cognitive functions, such as spatial working memory. The Y-maze and novel object recognition (NOR) tests are frequently used in research to study working memory however, the novel location / novel object recognition (NL/NOR) test was developed more recently to study hippocampal-dependent spatial memory. When treated with water soluble coenzyme-Q10, called ubisol-Q10, cell cultures expressing human mutant presenilin-1 (PSEN1) show reduced levels of β-amyloid and protection against harmful reactive agents. This research suggested that ubisol-Q10 may be an effective treatment for AD. The current study uses a double transgenic mouse model of AD expressing human mutant amyloid precursor protein (APP) and PSEN1 (1-1.5 year old male B6.Cg-Tg with APP/PSEN1) to investigate the effects of orally-administered ubisol-Q10 (fed 50 µg/mL in water supply starting at 1 month old) on tests of long-term memory and spatial working memory using modified Y-maze, NOR, and NL/NOR tests, compared to wild type mice (1-1.5 year old male C57BL/6J). Results using Repeated Measures ANOVA show that both wild type and ubisol-Q10 treated APP/PSEN1 mice perform better on tests of long-term memory and spatial memory compared to untreated APP/PSEN1 mice. The histopathological studies conducted after the behavioral tests confirm these results. Ubisol-Q10 treated APP/PSEN1 mice show remarkably low numbers of β-amyloid plaques in the hippocampus and cortex compared to untreated APP/PSEN1 mice. This study provides evidence to support the use of ubisol-Q10 treatment in AD and further research should continue to investigate the cognitive and neurobiological effects of ubisol-Q10
Home-range spillover in habitats with impassable boundaries: Causes, biases and corrections using autocorrelated kernel density estimation
No full textAn animal's home-range plays a fundamental role in determining its resource use and overlap with conspecifics, competitors and predators, and is therefore a common focus of movement ecology studies. Autocorrelated kernel density estimation addresses many of the shortcomings of traditional home-range estimators when animal tracking data are autocorrelated, but other challenges in home-range estimation remain. One such issue is known as ‘spillover bias’, in which home-range estimates do not respect impassable movement boundaries (e.g. shorelines and fences), and occurs in all forms of kernel density estimation. While several approaches to addressing spillover bias are used when estimating home ranges, these approaches introduce bias throughout the remaining home-range area, depending on the amount of spillover removed, or are otherwise inaccessible to most ecologists. Here, we introduce local corrections to home-range kernels to mitigate spillover bias in (autocorrelated) kernel density estimation in the continuous time movement model (ctmm) package, and demonstrate their performance using simulations with known home-range extents and distributions, and a real-world case study. Simulation results showed that local corrections minimized bias in bounded home-range area estimates, and resulted in more accurate distributions when compared with commonly used post hoc corrections, particularly at small–intermediate sample sizes. Comparison of the impacts of local vs. post hoc corrections to bounded home-ranges estimated from lake trout (Salvelinus namaycush) demonstrated that local corrections constrained the redistribution of probability mass within the remaining home-range area, resulting in proportionally smaller home-range areas compared with when post hoc corrections are used
Looking Back in Kindness: A Self-Compassion Exercise for Self-Relevant Unresolved Events
No full textMorphology and Composition of Brake Wear Particles Ameliorated by an Alumina Coating Approach
No full textA plasma-assisted electrochemical deposition (PAECD) technology was introduced to coat a cast iron brake disc for the possible reduction of brake wear and brake wear particle (BWP) emission. The majority of the coating consisted of alumina (Al2O3), determined by energy dispersive X-ray (EDX) analysis and X-ray diffraction (XRD) analysis. To validate the above strategy of the coating technology for automotive brake corners, one brake stock rotor was replaced by a PAECD-coated rotor for a vehicle road test. After the road test, weight loss of the brake components (rotors and pads) was measured, showing that the alumina coating can reduce the brake wear by more than 70%. BWPs were also collected from wheel barrels, spokes, and brake friction rings of the coated and uncoated rotors during the road test. A morphology and chemical composition analysis of the collected BWPs indicated that the coating could reduce BWP generation from the original sources and avoid a metal pick-up (MPU) issue, leading to less metallic content in BWPs. This alumina coating may provide the auto sector with a sustainable approach to overcome the brake dust emission problem, evidenced by less wear of the brake pads, minimal wear of the coated brake rotor, less MPUs, and a clean wheel rim on the coated brake corner
Pulling Order Back from the Brink of Disorder: Observation of a Nodal-Line Spin Liquid and Fluctuation Stabilized Order in K2IrCl6
No full textCompeting interactions in frustrated magnets can give rise to highly degenerate ground states from which correlated liquidlike states of matter often emerge. The scaling of this degeneracy influences the ultimate ground state, with extensive degeneracies potentially yielding quantum spin liquids, while subextensive or smaller degeneracies yield static orders. A long-standing problem is to understand how ordered states precipitate from this degenerate manifold and what echoes of the degeneracy survive ordering. Here, we use neutron scattering to experimentally demonstrate a new "nodal-line"spin liquid, where spins collectively fluctuate within a subextensive manifold spanning one-dimensional lines in reciprocal space. Realized in the spin-orbit-coupled, face-centered-cubic iridate K2IrCl6, we show that the subextensive degeneracy is robust, but remains susceptible to fluctuations or longer-range interactions which cooperate to select a magnetic order at low temperatures. Proximity to the nodal-line spin liquid influences the ordered state, enhancing the effects of quantum fluctuations that in turn act to stabilize the sublattice magnetization through the self-consistent opening of a large spin-wave gap. Our results demonstrate how quantum fluctuations can act counterintuitively in frustrated materials: Even in a case where fluctuations are ineffective at selecting an ordered state from a degenerate manifold, at the brink of the nodal spin liquid, they can act to protect the ordered state and dictate its low-energy physics
A review of recent AI applications in next-generation power electronics
No full textPower electronics (PELS) is an important part of modern technology by enabling energy conversion, control, and management, which is essential for powering renewable energy systems (RES), electric vehicles (EVs), industrial automation, and advanced consumer electronics, thereby driving sustainability and innovation. Consequently, the efficiency and performance of PELS components are always in priority. To this end, the potential applications of generative and non-metaheuristic AI-driven algorithms in the control, maintenance, and design of PELS systems are reviewed in this paper. Covering a spectrum of models, including generative adversarial networks (GANs), neural networks (NNs), quantum neural networks (QNNs), fuzzy interfaces, and reinforcement learning (RL), this paper investigates their applications in control, maintenance, and design of PELS. The review also provides the implications of big data, generative, and non-metaheuristic AI-driven algorithms in efficiency enhancement, reliability, and sustainability of PELS-integrated energy infrastructure. Also, some of the recently funded projects in the U.S. and Europe, as well as the associated challenges and future research directions, are investigated in this emerging sector
Magnon spectra of cuprates beyond spin wave theory
No full textThe usual starting point for understanding magnons in cuprate antiferromagnets such as La2CuO4 is a spin model incorporating cyclic exchange, which descends from a one-band Hubbard model, and has parameters taken from fits based on non-interacting spin wave theory. Here we explore whether this provides a reliable description of experiment, using matrix product states (MPS) to calculate magnon spectra beyond spin wave theory. We find that analysis based on low orders of spin wave theory leads to systematic overestimates of exchange parameters, with corresponding errors in estimates of Hubbard t/U. Once these are corrected, the "standard"model provides a good account of magnon dispersion and lineshape in La2CuO4, but fails to fully capture the continuum observed at high energies. The extension of this analysis to CaCuO2 and Sr2IrO4 is also discussed
A comprehensive review of the structural basis for the selectivity of sulfonamide-based inhibitors for carbonic anhydrase isoforms IX and XII over carbonic anhydrase II based on the available high quality crystallographic data
No full textHypoxia in solid tumours induces carbonic anhydrases (CAs) upregulation, notably CA IX and CA XII, to sustain pH homeostasis. While sulfonamide-based zinc binders show high affinity for these targets, achieving the required selectivity versus the ubiquitous CA II remains challenging. Fortunately, the efforts of the community in obtaining experimental structures of ligand-protein complexes have now generated sufficient samples to rationalize isoform preferences. Herein, we provide our detailed structure-annotated meta-analysis of sulfonamide binding across CA II, CA IX, and CA XII that standardizes residue numbering and interaction taxonomy. We examine 130 X-ray cocrystal structures, CA II (47), CA IX (55), and CA XII (28), to quantify Zn-sulfonamide geometry, entrance-zone contacts (Arg60, Thr199/Thr200, His64 π-cation), conserved water mediation, and occupancy/orientation within the 130s subpocket (residues 131/132/135) that provide the best opportunities for delivering selectivity. From these data, we extract concrete, structure-derived design rules: (i) lowering sulfonamide pKa boosts affinity across isoforms but does not confer selectivity; (ii) directing steric/hydrophobic bulk into the 130s subpocket exploits Phe131/Gly132/Val135 (CA II) versus Val131/Asp132/Leu135 (CA IX) versus Ala131/Ser132/Ser135 (CA XII) differences; (iii) favourable entrance-zone interactions, e.g., salt bridging to Arg60 (IX), halogen bonding to Thr199, and occasional His64 π-cation, enhances IX/XII bias; and (iv) compact, highly polar heads without tailored tails tend to default to preferring CA II. This critical synthesis consolidates the dispersed structural evidence into an isoform-resolved map of selectivity-enabling interactions. This provides public access to a very useful tool for CA IX/XII-selective inhibitor design.Natural Sciences and Engineering Research Council of Canada (Award: 2018-06338 & 2024-04113)University of WindsorUniversiti Malaya (Award: IIRG003A-2019
Navigating fragmented services: a gender-based violence (GBV) critical feminist analysis of women’s experiences engaging with health and social supports in three Canadian cities
No full textGender-based violence (GBV) remains a pervasive public health crisis with devastating impacts on women’s health and well-being. Women experiencing GBV face considerable barriers accessing appropriate and timely health and social services. This study explored women’s experiences with health and social services in three Canadian cities to understand critical challenges and strengths in service provision for women experiencing GBV. Methods: In-depth interviews were conducted with self-identifying women (n = 21) who had accessed health or social care services and with service providers (n = 25) in three Canadian cities between February 2021 and November 2022. Women’s interviews focused on experiences engaging with services including what worked well, the challenges they faced, and their recommendations to enhance service delivery to women experiencing violence. Staff interviews focused on their experiences of providing services within their organization, and the strengths and challenges in providing services to women within their community. Data were analyzed using reflexive thematic analysis with a gender-based violence critical feminist lens. Results: We organized the findings into three interrelated themes. First our results show how the systems within which health and social services are organized, are not designed to meet women’s complex needs, with rigid structures, siloed services, and stigmatizing cultures creating significant barriers. Second, the data illustrate how service providers support and empower women through practices such as providing key information, assisting with administrative tasks, offering material resources, and addressing discrimination through advocacy and accompaniment. Third, our findings demonstrate how building an effective working relationship characterized by trust, non-judgment, and collaboration is crucial for service engagement and women’s overall well-being. Conclusions: Findings illuminate critical public health challenges as women navigate fragmented services across multiple and siloed systems not designed to meet their complex needs. There is an urgent need for systemic change to create more integrated, responsive support systems for women experiencing GBV. This includes addressing underlying structures perpetuating gender inequities and violence. Facilitating safe access to holistic services that consider women’s preferences is crucial. Effective working relationships built on trust, respect, and power-sharing are key to supporting women’s agency and addressing their interconnected needs