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Cytological and Morphological Characteristics of the Genus Chloris
No full textChromosome number, method of reproduction and morphological characteristics were investigated in 14 species of the genus Chloris including Rhodes grass. Chromosome numbers of the Chloris species were 2n = 20 (gayana, roxburghiana, pilosa and virgata), 40 (gayana, pycnothrix, acicularis, radiata, polydactyla, divaricata and barbata), 80 (ciliata and distichophylla), 100 (castilloniana) and 120 (truncata). Method of reproduction was studied by embryo sac analysis. Embryo sacs of all tested species had eight nuclei, indicating sexuality. Selfed seed set indicated that Rhodes grass is cross-pollinated and the other species are self-pollinated. Cluster analysis was applied to numerical data of 26 morphological characters. Thirty-four strains tested were classified into 7 groups. Each group tended to have species with the same ploidy level. The stomata of truncata (12x), castilloniana (lOx) and distichophylla (8x) were the largest of all species tested. The relationships between ploidy levels and morphological characteristics were not always consistent
Comparison of Energy Conversion During Forage Production and Supplemental Investment Efficiencies in Different Livestock Feed Production Systems
No full textSolar and supplemental energy dynamics were compared for several years in three different livestock feed production systems including, a) double cropping with barley and corn for whole-crop-silage, b) perennial cutting meadow of orchardgrass for hay-making, and c) grazing by fattening Holsteins with six cool-season grasses. The results obtained are; (1) In the double cropping system, the plot receiving slurry manure (S2) maintained the highest energy yield (3.86xl05MJ, 92,350 Meal of energy for each hectare of land, or 0.94% of overall efficiency as compared to global solar radiation) throughout the 5-year experimental period. (2) From the orchardgrass meadow, 1. 93x105MJ, 46,130 Meal/ha of energy yield (0.47% of overall efficiency) was observed in the plot with chemical fertilizer application (Hl). (3) While in the grazing grassland, 1.36x105MJ, 32,490 Meal/ha of energy (0.33% of overall efficiency) was harvested by grazing (Pl). (4) These differences in feed production systems were reduced at the digestible energy yield level, as, S2: 0.51 %, Hl: 0.28% and Pl: 0.23%, respectively. (5) Output/Input ratios were low when chemical fertilizer was applied, and high in plots to which barnyard manure was applied. ( 6) Output/Input ratios at digestible energy levels in the grazing plots were close to the highest efficiency
The mitochondria as an emerging target of self- renewal in T-cell acute lymphoblastic leukemia
No full textAcute lymphocytic leukemia (ALL) is the most common leukemia in children, with the T-cell subtype (T- ALL) accounting for 15% of those cases. Despite advancements in the treatment of T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to the inability of chemotherapy agents to eradicate leukemia stem cells (LSC), which possess self-renewal capabilities and are responsible for the long-term maintenance of the disease. Mitochondria have been recognized as a therapeutic vulnerability for cancer stem cells, including LSCs. Mitocans have shown promise in T-ALL both in vitro and in vivo, with some currently in early-phase clinical trials. However, due to challenges in studying LSCs in T-ALL, our understanding of how mitochondrial function influences self-renewal remains limited. This review highlights the emerging literature on targeting mitochondria in diverse T-ALL models, emphasizing specific mitochondrial vulnerabilities linked to LSC self-renewal and their potential to significantly improve T-ALL treatment
Enhancing The Sustainability of Thermally Induced Phase Separation and Non-Solvent-Induced Phase Separation Techniques for Membrane Fabrication
No full textMembranes are widely used in industrial applications to provide an alternative separation technique to thermally driven separations. Ultrafiltration membranes, in particular, are typically made using phase separation techniques, such as thermally induced phase separation (TIPS) and non-solvent-induced phase separation (NIPS). However, these membrane fabrication strategies pose significant environmental challenges due to the use of hazardous solvents and high energy consumption. This dissertation aims to enhance the sustainability of membrane fabrication by utilizing eco-friendly solvents as such as terpineol, non-toxic plant-based solvent, commonly found in perfumes and cosmetics, and Rhodiasolv® PolarClean, a byproduct of Nylon-66 production that also has a low-hazard profile. Additionally, this research explores the use of recycled plastics.
The first study of this dissertation successfully investigated the impact of the small molecules as additives on the polystyrene terpineol system exhibiting an upper critical solution temperature (UCST). This research highlights a new path to reduce the phase transition temperature for TIPS by managing hydrogen bonding interactions and polymer solubility by decreasing the transition from 65 °C to room temperature. This approach allows membrane formation at room temperature, resulting in lower energy consumption. The fabricated membranes were characterized by analyzing their pore size, morphology, and filtration performance, showing comparable or improved properties over conventionally fabricated membranes.
The second study investigated the fabrication of poly(acrylonitrile-co-butadiene-co-styrene) (ABS) membrane using green solvent and the effect of the diluents on the ABS membrane. Rhodiasolv® PolarClean was used as the primary solvent, and ethanol and acetone were used as additives to study the fabrication of ABS membrane using the NIPS. Using PolarClean as the primary solvent and varying the additive ratios allowed for the control of the membrane morphology and performance. Whereas, using only PolarClean for fabrication ABS resulting fingerlike pore morphology and relatively low bovine serum albumin (BSA) rejection. The additive addition impacts the volatility and stability of the system therefore impacting the kinetic phase inversion, and membrane morphology.
In the third study, recycled polymers from LEGO® blocks, including high impact polystyrene (HIPS), ABS, and poly(methyl methacrylate-co-acrylonitrile-co-butadiene-co-styrene) (MABS), were employed to fabricate membrane via NIPS . There are limited studies of the impact of different polarity segments in HIPS, ABS, and MABS on phase separation of recycled polymer membranes. Membranes were fabricated from recycled LEGO blocks using NIPS with Rhodiasolv® PolarClean and acetone. Blending MABS and ABS allowed to control the ratio of acrylonitrile and methyl methacrylate in the sample. The increase in the ratio of MABS in the blended samples altered the membrane structure from sponge-like to finger-like, likely due to the increased hydrophilicity attributed to the polar block, which allowed water to penetrate as a nonsolvent and caused growth in the lean polymeric phase, resulting in a stretched finger-like sublayer. Blended membranes exhibited only modest changes in their thermal stability and tensile strength, likely due to the similar chemical structures of some segments.
Overall, this dissertation establishes that the sustainability of the membrane fabrication can be improved using small molecular weight additives, green solvent, and recycled polymers resulting in more environmentally friendly polymeric membranes with comparable performance to conventionally synthesized structures
CHARACTERIZING AND TARGETING THE NON-CATALYTIC FUNCTIONS OF PHOSPHATASE OF REGENERATING LIVER 3 (PRL-3) IN ONCOGENESIS AND CANCER PROGRESSION
No full textPhosphatase of Regenerating Liver 3 (PRL-3) is frequently upregulated in various cancers and is associated with poor patient prognosis. Although traditionally studied for its phosphatase activity, PRL-3 also interacts with the CNNM family of magnesium transporters through its catalytic site, and these two functions are mutually exclusive at any given time. Most previous studies relied on a commonly used PRL-3 mutation that disrupts both phosphatase activity and CNNM binding, making it challenging to determine which function drives its oncogenic effects. To address this gap in the field, I utilized a panel of PRL-3 mutants that selectively disrupt either phosphatase activity or CNNM binding to assess the contribution of each function to cancer progression. These mutants were evaluated in transgenic zebrafish models of acute lymphoblastic leukemia and rhabdomyosarcoma, as well as several human cancer cell lines. I examined phenotypes associated with tumor progression and metastasis, including leukemogenesis, tumor burden, self-renewal, migration, invasion, and resistance to apoptosis. Across all models, wild-type PRL-3 and the phosphatase-inactive mutant produced similar oncogenic effects, while the CNNM-binding-deficient mutant did not enhance disease progression. These results indicate that PRL-3 promotes cancer progression independently of its phosphatase activity, likely through its interaction with CNNM proteins. To further explore this mechanism, I investigated the effects of PRL-3 in colon cancer cells. PRL-3 overexpression did not alter proliferation rates but enhanced survival under stress conditions, including hypoxia, acidification, and nutrient deprivation, in a manner that did not require phosphatase activity. PRL-3 overexpression also altered intracellular magnesium content, leading to aberrant accumulation. RNA sequencing and untargeted metabolomics of cells expressing different PRL-3 mutants revealed significant changes in metabolism, apoptosis resistance, and epithelial-to-mesenchymal transition. These alterations were present in cells expressing wild-type or phosphatase-inactive PRL-3 but not in the CNNM-binding-deficient mutant, implicating the CNNM interaction and magnesium disruption as central to PRL-3’s effects. Further metabolic profiling demonstrated that PRL-3 enhanced glycolysis, increased cystine uptake, and elevated alanine synthesis, and metabolic adaptations that support survival in hostile environments. Finally, I developed an in vitro FRET-based assay to rapidly evaluate the ability of molecules to disrupt the PRL:CNNM interaction. Using this assay, I discovered that existing PRL-3 inhibitors suppress phosphatase activity but fail to disrupt CNNM binding, which may explain their limited success in preclinical models. I adapted this assay for a high- throughput system and screened a library of drug fragments, along with a panel of in silico-docked compounds. By pairing these results with a thermal stability assay, we identified a handful of compounds that could bind to PRL-3 and significantly reduce its ability to bind CNNMs in vitro. These findings serve as promising leads for future drug development campaigns. Together, these findings indicate that the oncogenic activity of PRL-3 is not a result of its phosphatase activity. Instead, these effects are likely a consequence of its non-catalytic activity, such as binding to CNNMs. This interaction promotes cancer cell survival under stress, likely by disrupting magnesium homeostasis and rewiring cellular metabolism. These results suggest a shift in drug development strategies toward targeting the non-catalytic functions of PRL-3, providing a new platform to support the discovery of compounds that can inhibit this previously underappreciated aspect of its function
You’re Too Slow! Self-Selected Volitional Efforts Reveal Unexploited Neuromuscular Reserve Capacity Compared to Maximal Efforts During Fatiguing, Load Equated Resistance Exercise
No full textThis investigation examined how movement intent influences neuromuscular excitation strategies during fatiguing resistance exercise, comparing maximal intended concentric efforts versus self-selected volitional efforts during load-equated Smith machine back squat exercise to quantify reserve capacity and characterize underlying neuromuscular mechanisms. Twenty-three resistance-trained participants (12 males, 11 females) completed a repeated-measures design, with replication, across six visits, performing smith machine back squat repetitions-to-failure at 70% 1RM under maximal intent (accelerate rapidly) and volitional intent (self-selected effort) conditions. Maximal voluntary isometric contractions used rapid (instantaneous 10-second effort) and ramp (5-second build-up, 5-second maximal) protocols. Surface electromyography (sEMG) was recorded from vastus lateralis and rectus femoris, with surface mechanomyography (sMMG) from rectus femoris only. Vastus lateralis underwent wavelet-based spectral decomposition to characterize high- and low-frequency contributions, while rectus femoris employed multimodal analysis of conventional signal characteristics. Performance measures included mean propulsive concentric velocity (MPCV), total repetitions, and peak force. Movement intent significantly influenced both force production and neuromuscular activation patterns. During MVIC trials, peak force differed between conditions (F(1,157.08) = 5.97, p = 0.02), suggesting that intent modulates even maximal voluntary efforts. This effect was accompanied by complex neuromuscular adjustments in both muscles examined. Vastus lateralis spectral analysis revealed that the interaction between condition, time, and frequency components was significant (F(1,23326.00) = 8.68, p \u3c 0.01), with mean frequency showing distinct temporal patterns between conditions (F(1,23330.00) = 39.03, p \u3c 0.01). Similarly, rectus femoris demonstrated comprehensive changes across all measured parameters, with significant condition × time interactions for both electrical (sEMG total intensity: F(1,23330.00) = 39.03, p \u3c 0.01; mean frequency: F(1,11403.02) = 41.85, p \u3c 0.01) and mechanical (sMMG total intensity: F(1,11687.01) = 316.02, p \u3c 0.01; mean frequency: F(1,11686.93) = 40.36, p \u3c 0.01) signals. Notably, sex differences emerged specifically for mechanical signal intensity (F(1,22.01) = 26.12, p \u3c 0.01), suggesting differential muscle mechanics between males and females. During repetitions-to-failure trials, performance differences between conditions became more pronounced. MPCV showed a significant condition × repetition interaction (F(1,2508.49) = 158.32, p \u3c 0.01), indicating divergent fatigue trajectories between maximal and volitional efforts. Males consistently achieved higher velocities than females (F(1,22.37) = 29.13, p \u3c 0.01) and completed fewer total repetitions (F(1,22.13) = 8.32, p \u3c 0.01), suggesting a trade-off between power output and endurance. These performance differences were supported by distinct neuromuscular strategies. Vastus lateralis displayed frequency-specific adaptations, with significant three-way interactions between condition, frequency band, and repetition number (F(1,5108.00) = 4.59, p = 0.03), while mean frequency shifted differently across conditions as fatigue progressed (F(1,5111.99) = 14.37, p \u3c 0.01). Sex differences in spectral intensity (F(1,22.00) = 5.08, p = 0.03) further highlighted physiological variations between males and females. Rectus femoris showed complementary patterns, with electrical signal frequency modulated by both condition and fatigue state (F(1,2541.94) = 5.64, p = 0.02), while signal intensity increased with fatigue regardless of intent (sEMG: F(1,2541.99) = 69.09, p \u3c 0.01; sMMG: F(1,2541.72) = 5.14, p = 0.02). The mechanical signals were particularly sensitive to movement intent, with mean frequency showing main effects for condition (F(1,2543.23) = 28.90, p \u3c 0.01), repetition (F(1,2542.85) = 32.39, p \u3c 0.01), and sex (F(1,21.84) = 10.13, p \u3c 0.01), indicating that movement intent fundamentally alters motor unit recruitment and firing patterns throughout the fatigue process. Movement intent produces systematic, frequency-dependent neuromuscular alterations during resistance exercise, though interpretation requires consideration of analytical limitations. MVIC force differences likely reflect methodological constraints rather than physiological differences. Repetitions-to-failure trials revealed that individuals operate substantially below maximal capabilities during volitional efforts, maintaining considerable reserve capacity while reaching similar physiological endpoints. Distinct spectral patterns suggest different energy distribution strategies: maximal efforts employ immediate front-loaded excitation, while volitional efforts utilize progressive intensification as fatigue accumulates. The rectus femoris multimodal analysis demonstrated systematic condition-related differences across both sEMG and sMMG measures, though the multifactorial nature of surface myographic signal generation precludes definitive attribution to specific motor unit control mechanisms. While results align with longitudinal evidence supporting maximal intent training for strength adaptations, practical considerations regarding adherence and ecological validity must balance physiological optimization
The Computational Algebra of Conformal Blocks
No full textConformal blocks are objects in quantum field theory that arise from conformal trans- formations, which are symmetries that preserve angles but not length. This aspect of conformal field theory has various interactions with algebraic geometry.
In this dissertation, we explore the underlying algebra and geometry of spaces and algebras of conformal blocks over SLn. We then use this information along with techniques from combinatorial commutative algebra, algebraic geometry, and representation theory to find a presentation of the algebra of SL4-conformal blocks. With this presentation, we then use computational methods to learn about some of the geometric properties of this algebra
Therapeutic applications of a novel humanized monoclonal antibody targeting chemokine receptor CCR9 in pancreatic cancer
No full textThe relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C–C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 cells, NK cell-mediated cytotoxicity was promoted by SRB2. Dose-dependent SRB2 cytotoxicity was observed in PDAC PDOs. In patient-derived xenograft mouse models, cytotoxicity of SRB2 monotherapy and in combination with oxaliplatin was also shown. In humanized immune-competent mouse models, SRB2 efficacy was similar to other drugs, but two mice in this cohort had complete tumor regression. Our current studies suggest that therapeutic targeting of CCR9 may improve PDAC outcomes, and additional studies are underway to evaluate SRB2 for clinical use
ARTIFICAL SPIN LATTICES CHARACTERIZED THROUGH MAGNETO OPTIC KERR EFFECT AND X-RAY DIFFRACTION
No full textThe future of computing has consistently been pushing toward faster and smaller devices, but as we approach the physical limitations of conventional electronics, new avenues must be explored. Traditional electronic computing, which relies on electrical charge, suffers from significant energy dissipation due to electron scattering and faces increasing challenges as transistor dimensions shrink into the quantum regime. One alternative method is magnetic computing, in contrast, which manipulates spin states rather than charge, offering benefits ranging from energy efficiency, non-volatility, and reduced heat generation. Arrays of magnetic nano-islands, arranged in artificial spin ice geometries, offer a way to explore these advantages, potentially leading the way for new, low-power computing through emergent magnetic behavior and spin-based logic. In this research, the process by which these arrays of magnetic nano-islands are fabricated using electron beam lithography and deposition is explored. It further characterizes the magnetic dynamics using the magneto-optic Kerr effect and X-ray diffraction. This study focuses on how the thickness and geometry of islands impact the dynamics of the magnetic moments within these islands
Crossing Borders, Breaking Barriers: The Transformative Journey of First-Generation Students Abroad
No full textFirst-generation students are underrepresented in study abroad programming, both nationally and at the University of Kentucky. To address participation barriers and the resulting opportunity gap for first-generation students, the University of Kentucky designed and implemented an innovative study abroad program for first-generation students titled “Explore First: Careers, Cultures, and Connections.” This specially-designed program sought to provide participants with the academic, social, and professional benefits associated with education abroad experiences, including greater self-efficacy, sense of belonging, intercultural competence, and career exploration and preparation. This mixed methods study examines these intended outcomes of Explore First. Drawing from quantitative surveys administered pre-, mid- and post-program, participant observation, and onsite daily written reflections, findings from this study demonstrate the effectiveness of the Explore First program in developing students’ self-efficacy and intercultural competence. Furthermore, Explore First also provided the students with the opportunity to increase their career preparation by facilitating meaningful learning experiences onsite through engagement with local companies. This study has implications for international education more broadly as it will help higher education administrators recognize the challenges these students face and inform the development of innovative support programs that are more inclusive and responsive to the specific needs of first-generation college students. As an innovative approach to study abroad program design and implementation, it is important to understand what and how students learn on Explore First, and how such innovative programs can be fully utilized to support first-generation students. As prior research has shown, and this study reinforces, once first-generation students acquire effective tools and support, they are capable and will continue to bridge the educational gap