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    Communiquons

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    This book has been made possible by the support of the University of Kansas’ Department of French, Francophone and Italian studies, the Open Language Resource Center, and a grant from the University of Kansas Libraries OER Grant Initiative.This book, Communiquons, is a clone of Le Pont, a OER book written for 3rd year courses. Communiquons’s goal was to simplify and change some of the texts and add some steps to make the grammar more accessible to fourth semester students. There was also a need for exercises in vocabulary and listening for these students which are sequenced throughout each chapter. The curriculum requires students to analyze target structures within context and make their own observations about when and how those structures are used. This inductive method is enhanced by online computer-graded activities that provide immediate feedback for students to track their own comprehension.This online component allows students to practice skills as well as grammatical and vocabulary structures outside of class. Providing students with this preview of the target structures will allow learning through a flipped model, freeing up class time to work on more open-ended communicative activities that explore the Francophone world. The structured format also allows the instructor to support students in areas which they find difficult. After completing a range of oral activities during class, the learner will move on to exercises that move them from input/discrimination activities (which are missing in many curricula) to comprehension/processing activities and eventually to production exercises. Communiquons is intended to reinforce structures that students have already started to acquire, while adding in further detail and new structures. It also promotes cultural understanding of the varied groups of people who share French as a common langage, and introduction to literary and cultural texts designed to show the grammar in focus in context.U. S. Department of Education grant P229A18000

    Factors Affecting Traffic Crash Survivors’ Accessibility to a Trauma Center within the Golden Hour

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    The Golden Hour has been used as an ideal measure of patients’ access to trauma centers. It isthe one hour after any traumatic event, including a traffic crash. It was shown that if patients canarrive at the hospital within one hour after a traumatic injury, the chances for survival increase.Therefore, this study aimed to identify the determining factors for patients involved in a trafficcrash to arrive at the trauma center within the Golden Hour. For this, four years (2018-2021) ofKansas traffic crash data were investigated. Among the eight factors analyzed in the study, thetime of the crash and lighting conditions were found to be the most important factors. The resultshowed that crashes that occurred when it was dark with no streetlights experienced the highesttotal transport time (TTT), which was 61.3 minutes. It may be an indication that crashes withlonger TTT occurred in rural remote locations. TTT did not exceed the Golden Hour for anyother factor. This study also showed that the distance between the crash location and the traumacenter was not the only factor for increased total transport time (TTT). For example, crashesoccurring within 5 miles of trauma centers can experience TTT higher than 60 minutes. Thiscould happen if a crash goes unnoticed for a long period of time or if time is needed to extricatethe patients

    Small Heterodimer Partner Modulates Macrophage Differentiation during Innate Immune Response through the Regulation of Peroxisome Proliferator Activated Receptor Gamma, Mitogen-Activated Protein Kinase, and Nuclear Factor Kappa B Pathways

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    A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Hepatic macrophages act as the liver’s first line of defense against injury. Their differentiation into proinflammatory or anti-inflammatory subpopulations is a critical event that maintains a delicate balance between liver injury and repair. In our investigation, we explored the influence of the small heterodimer partner (SHP), a nuclear receptor primarily associated with metabolism, on macrophage differentiation during the innate immune response. During macrophage differentiation, we observed significant alterations in Shp mRNA expression. Deletion of Shp promoted M1 differentiation while interfering with M2 polarization. Conversely, overexpression of SHP resulted in increased expression of peroxisome proliferator activated receptor gamma (Pparg), a master regulator of anti-inflammatory macrophage differentiation, thereby inhibiting M1 differentiation. Upon lipopolysaccharide (LPS) injection, there was a notable increase in the proinflammatory M1-like macrophages, accompanied by exacerbated infiltration of monocyte-derived macrophages (MDMs) into the livers of Shp myeloid cell specific knockout (Shp-MKO). Concurrently, we observed significant induction of tumor necrosis factor alpha (Tnfa) and chemokine (C-C motif) ligand 2 (Ccl2) expression in LPS-treated Shp-MKO livers. Additionally, the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways were activated in LPS-treated Shp-MKO livers. Consistently, both pathways were hindered in SHP overexpression macrophages. Finally, we demonstrated that SHP interacts with p65, thereby influencing macrophage immune repones. In summary, our study uncovered a previously unrecognized role of SHP in promoting anti-inflammatory macrophage differentiation during the innate immune response. This was achieved by SHP acting as a regulator for the Pparg, MAPK, and NF-κB pathways. Keywords: nuclear receptor; small heterodimer partner (SHP); knockout; macrophage; differentiatio

    Chromosome-level genome assembly of Hydractinia symbiolongicarpus

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    Hydractinia symbiolongicarpus is a pioneering model organism for stem cell biology, being one of only a few animals with adult pluripotent stem cells (known as i-cells). However, the unavailability of a chromosome-level genome assembly has hindered a comprehensive understanding of global gene regulatory mechanisms underlying the function and evolution of i-cells. Here, we report the first chromosome-level genome assembly of H. symbiolongicarpus (HSymV2.0) using PacBio HiFi long-read sequencing and Hi-C scaffolding. The final assembly is 483 Mb in total length with 15 chromosomes representing 99.8% of the assembly. Repetitive sequences were found to account for 296 Mb (61%) of the total genome; we provide evidence for at least two periods of repeat expansion in the past. A total of 25,825 protein-coding genes were predicted in this assembly, which include 93.1% of the metazoan Benchmarking Universal Single-Copy Orthologs (BUSCO) gene set. 92.8% (23,971 genes) of the predicted proteins were functionally annotated. The H. symbiolongicarpus genome showed a high degree of macrosynteny conservation with the Hydra vulgaris genome. This chromosome-level genome assembly of H. symbiolongicarpus will be an invaluable resource for the research community that enhances broad biological studies on this unique model organism

    Fungal secondary metabolism is governed by an RNA-binding protein CsdA/RsdA complex

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    Production of secondary metabolites is controlled by a complicated regulatory network in eukaryotic cells. Several layers of regulators are involved in this process, ranging from pathway-specific regulation, to epigenetic control, to global regulation. Here, we discover that interaction of an RNA-binding protein CsdA with a regulator RsdA coordinates fungal secondary metabolism. Employing a genetic deletion approach and transcriptome analysis as well as metabolomics analysis, we reveal that CsdA and RsdA synergistically regulate fungal secondary metabolism comprehensively. Mechanistically, comprehensive genetic and biochemical studies prove that RsdA and CsdA co-localize in the nucleus and physically interact to achieve their functions. In particular, we demonstrate that CsdA mediates rsdA expression by binding specific motif “GUCGGUAU” of its pre-mRNA at a post-transcriptional level. We thus uncover a mechanism in which RNA-binding protein physically interacts with, and controls the expression level of, the RsdA to coordinate fungal secondary metabolism

    Low heat tolerance and high desiccation resistance in nocturnal bees and the implications for nocturnal pollination under climate change

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    Predicting insect responses to climate change is essential for preserving ecosystem services and biodiversity. Due to high daytime temperatures and low humidity levels, nocturnal insects are expected to have lower heat and desiccation tolerance compared to diurnal species. We estimated the lower (CT) and upper (CT) thermal limits of Megalopta, a group of neotropical, forest-dwelling bees. We calculated warming tolerance (WT) as a metric to assess vulnerability to global warming and measured survival rates during simulated heatwaves and desiccation stress events. We also assessed the impact of body size and reproductive status (ovary area) on bees' thermal limits. Megalopta displayed lower CT, CT, and WTs than diurnal bees (stingless bees, orchid bees, and carpenter bees), but exhibited similar mortality during simulated heatwave and higher desiccation tolerance. CT increased with increasing body size across all bees but decreased with increasing body size and ovary area in Megalopta, suggesting a reproductive cost or differences in thermal environments. CT did not increase with increasing body size or ovary area. These results indicate a greater sensitivity of Megalopta to temperature than humidity and reinforce the idea that nocturnal insects are thermally constrained, which might threaten pollination services in nocturnal contexts during global warming

    Experimental and numerical investigation of hydrocarbon gas huff-n-puff in unconventional reservoir

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    Unconventional resources have become an important and irreplaceable part of the energy supply for industry and the public. The Eagle Ford play in Texas has been one of the most productive unconventional reservoirs in North America. To continue unlocking potential barrels of oil from unconventional reservoirs, research and development of production technology and understanding of production mechanisms are the top priorities. Gas huff-n-puff injection technique has been attracting industry interest because of the convenience, efficiency, and potential of carbon sequestration. This dissertation focuses on studying the phase behavior, mass transfer mechanism, and operation parameters during hydrocarbon gas huff-n-puff injection in the Eagle Ford play. It included several parts.First, phase behavior between injection gas and reservoir stock-tank oil was analyzed experimentally and numerically. A pressure-volume-temperature (PVT) cell was used for phase behavior experiments between oil and gas fluid systems, CMG WinProp™ software was used to tune heavy components’ critical properties as well as other Peng-Robinson equation of state (PR-EOS) properties, and CMG GEM was used for minimum miscibility pressure (MMP) slim tube modelling. Accurate characterization of reservoir fluids in refined EOS models and MMP for huff-n-puff injection pressure design were studied.Second, experimental measurement and analysis of pressure, oil recovery factor, and produced fluid compositions from six cycles of hydrocarbon gas huff-n-puff injection in three Eagle Ford core samples at reservoir conditions were conducted. The recovery factors for the three samples were 57.5%, 56.7%, and 51.7%, respectively. A significant gap existed in defining diffusion coefficients coupled with rock tortuosity. Numerical study with focuses on fracture complexity, lithological variations, and diffusion mechanism was carried out by history matching model to experimental data at the core scale in Schlumberger ECLIPSE®. A comprehensive study was performed on three representative litho-facies from Lower Eagle Ford rock samples to measure effective within phase and cross-phase diffusion coefficients.Third, the numerical model was scaled up from core scale to field scale for sensitivity analysis and predictions in Schlumberger PETREL. The field model was history matched with huff-n-puff pilot test in the Eagle Ford then diffusion mechanism was incorporated with the model. 2.2% higher oil recovery factor was observed by adding diffusion mechanism in the simulation model for five cycles of hydrocarbon gas huff-n-puff. Smaller fracture spacing promoted diffusion mechanism leading to higher oil recovery. Depletion level prior to huff-n-puff injection for the producer also affected ultimate recovery efficiency with an optimum time for each case of live and dead oil systems. Parameter analysis on puff production periods and soaking times suggested that longer production time per cycle slightly increased oil production, while shorter soaking time accelerates oil production and had minimal difference in ultimate oil recovery after huff-n-puff. Injection gas comparisons ranked y-grade CO2 ≈ hydrocarbon gas lean gas for maximizing oil production. The study contributes insights into upscaling and offers huff-n-puff pilot design recommendations in the Eagle Ford formation

    The RNA-binding Protein HuR in Cancer Immune Evasion: Mechanisms and Therapeutic Implications

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    RNA-binding protein (RBP) HuR is upregulated in multiple types of cancer and the elevated HuR is associated with high-grade tumors and poor clinical outcomes. HuR forms a complex network of interactions with target mRNAs through the recognition and binding to the adenylate-uridylate-rich elements (AU-rich elements; AREs) in their 3′-untranslated region (3′-UTR). By regulating the expression of proto-oncogenes, cytokines, and other regulatory proteins involved in various cancer hallmarks, HuR promotes tumorigenesis and cancer progression.Cancer immunotherapy, particularly the immune checkpoint blockade (ICB) represents a revolutionary advance in cancer treatment. However, only a subset of patients responds to ICB. Response rates to ICB in breast cancer, lung cancer, and prostate cancer patients are notably low. ICB targeting Programmed cell death-1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) has greatly improved clinical outcomes in diverse human cancers. However, a more thorough understanding of the mechanisms underlying low immunogenicity in these tumors is crucial to address remaining issues, including the low objective response rates in patients.In this study, we investigate the involvement of HuR in T cell activation and demonstrated that HuR knockout in cancer cells reduced PD-L1 proteins and enhanced T cell activation. We identified HuR as a novel regulator of PD-L1 and CD147 by directly binding to the 3′-UTR of their mRNA, thereby promoting their stability. Given the immunosuppressive functions of PD-L1 and CD147 in cancer, we hypothesized that functional inhibition of HuR could be a promising approach to enhance ICB efficacy. We repurposed the anti-helminthic drug niclosamide as a HuR inhibitor and discovered that it decreased PD-L1 protein levels and glycosylation by inhibiting the nucleo-cytoplasmic translocation of HuR. Niclosamide enhanced T cell-mediated killing of cancer cells and significantly improved the efficacy of anti-PD-1 immunotherapy in breast and lung syngeneic animal tumor models. To further explore the role of HuR in cancer immune evasion through CD147 regulation, we developed a HuR-specific small molecular inhibitor, KH-39, which disrupts the interaction between HuR and its target mRNAs. KH-39 effectively inhibits CD147 expression and its associated cytokine IL-6. We established a combination strategy using HuR inhibitor KH-39 and anti-PD-1 antibody to enhance the ICB response rate in a murine breast cancer model. The combination approach demonstrated substantial tumor growth inhibition and significantly improved overall survival compared to the single-agent treatments. In conclusion, this dissertation research expands our understanding of the biological role of HuR in tumor immune evasion. It provides a strong proof-of-principle of targeting HuR to modulate its downstream signaling to enhance the response of ICB immunotherapy, particularly in immune “cold” cancers.

    Development of Large High-Strength Reinforcing Bars with Standard Hooks and Heads

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    Hooked and headed reinforcing bars are viable alternatives for development of reinforcing steel when member geometry does not allow for a straight deformed bar to fully develop its yield strength. Current design provisions in ACI 318-19 Building Code impose limitations on the use of hooked and headed bars larger than No. 11 (that is, No. 14 and No. 18 bars), mainly due to a lack of experimental data. This research continues a comprehensive study of the anchorage and development of high-strength hooked and headed bars to expand the available data to include No. 14 and No. 18 bars. Forty-two large-scale simulated beam-column joint specimens containing No. 11, No. 14 and No. 18 hooked and headed bars are tested. Of the 42 specimens, 12 contain hooked bars and 30 contain headed bars. The effects of bar size, bar spacing, bar location, embedment length, confining transverse reinforcement in the joint region, placement of bars within the cross-section, concrete compressive strength, compression strut angle, and effective beam depth on anchorage strength are investigated. Two loading conditions are used. In loading condition A, the joint shear is 80% of the total applied force to the bars, simulating the forces in an exterior beam-column joint with the beam located at the midheight of the column. The joint shear is reduced to ⁓69% of the total applied force in loading condition B. All hooked bar specimens and 15 headed bar specimens are tested under loading condition A, while the other 15 headed bar specimens are tested using loading condition B. Concrete compressive strengths range from 6,390 to 15,770 psi for hooked bars and from 5,310 to 16,210 psi for headed bars. Bar stress at failure ranges from 87,300 to 130,600 psi for hooked bars and from 54,900 to 148,300 psi for headed bars. Center-to-center bar spacing, s, ranges from 3.5db to 10.6db for hooked bars and from 2.7db to 10.6db for headed bars, where db is the nominal hooked or headed bar diameter. Confining reinforcement, Ath, or parallel ties, Att, in the joint region ranges from 0 to 0.465Ahs and 0 to 0.827Ahs for hooked and headed bars, respectively, where Ath or Att equal the total cross-sectional area of tie legs within 10db from the top of the bars and Ahs is the total area of the bars being developed. Headed bars with net bearing areas between 4.2 and 4.4 times the bar area are used. The test results are compared with the current provisions for the development length of hooked and headed bars in Chapter 25 of ACI 318-19. Descriptive equations to characterize anchorage strength of hooked and headed bars developed previously for No. 11 and smaller bars are evaluated. New descriptive equations are developed to represent the anchorage strength for bars as large as No. 18. The equations are compared with the test results in the current study and available in the literature. New design provisions for development length are developed for hooked and headed bars and evaluated with respect to test results and ACI 318-19 provisions. The descriptive equations for hooked and headed bars developed in this study accurately account for concrete compressive strength, confining reinforcement, and bar spacing. The ability of the equations to accurately represent anchorage strength is insensitive to variations in compression strut angle and effective beam depth. While the contribution of confining reinforcement to anchorage strength increases with bar size, the effect of increasing confining reinforcement for headed bars is much lower than for hooked bars and much lower for headed bars than observed in prior studies. Under loading condition A, all hooked bar specimens, even those without confining reinforcement, carried the joint shear and exhibited an anchorage failure, whereas shear-like failures were observed in some headed bar specimens under similar conditions. These observations reveal the distinct role of the tail of the hook in helping to carry the joint shear, and indicate the difference in joint shear under loading conditions A and B is a key factor in the type of failure and anchorage strength of headed bars. Larger headed bars need confining reinforcement on the order of 0.5Ahs to carry the joint shear demand under loading condition A. The development length provisions in ACI 318-19 are unnecessarily conservative for No. 14 and No. 18 hooked and headed bars. For both hooked and headed bars, providing confining reinforcement below the minimum amounts required by ACI 318-19 contributes to anchorage strength. Similar to No. 11 and smaller hooked and headed bars, the effect on anchorage strength of concrete compressive strength is best represented by the 0.25 power for design. The bar location factor o of 1.25 in ACI 318-19, applied to bars terminating inside column longitudinal reinforcement (column core) with side cover < 2.5 in. or bars with side cover < 6db, can be safely reduced to 1.15 for design. The proposed design equations for hooked and headed bars are applicable to concrete with compressive strengths up to 16,000 psi, steel with yield strengths up to 120,000 psi, and bars as large as No. 18. The proposed modification factors for confining reinforcement (expressed as Ath/Ahs or Att/Ahs) and bar spacing (expressed as s/db), in the form of a single expression or simplified expressions that address the effects of confining reinforcement and bar spacing independently, provide more flexibility for designers to take advantage of a range of values for Ath/Ahs or Att/Ahs and s/db and, ultimately, permit the use of shorter development lengths than the provisions in ACI 318-19 for all bar sizes.Charles Pankow Foundation Research Grant Agreement #05-18, D17ACI FoundationBarSplice ProductsHeaded Reinforcement CorporationnVENT LentonCRSI Education and Research FoundationPrecast/Prestressed Concrete InstituteCommercial Metals CompanyNucor Corporatio

    Characterization of Volatile and Particulate Emissions from Desktop 3D Printers

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    The rapid expansion of 3D printing technologies has led to increased utilization in various industries and has also become pervasive in the home environment. Although the benefits are well acknowledged, concerns have arisen regarding potential health and safety hazards associated with emissions of volatile organic compounds (VOCs) and particulates during the 3D printing process. The home environment is particularly hazardous given the lack of health and safety awareness of the typical home user. This study aims to assess the safety aspects of 3D printing of PLA and ABS filaments by investigating emissions of VOCs and particulates, characterizing their chemical and physical profiles, and evaluating potential health risks. Gas chromatography-mass spectrometry (GC-MS) was employed to profile VOC emissions, while a particle analyzer (WIBS) was used to quantify and characterize particulate emissions. Our research highlights that 3D printing processes release a wide range of VOCs, including straight and branched alkanes, benzenes, and aldehydes. Emission profiles depend on filament type but also, importantly, the brand of filament. The size, shape, and fluorescent characteristics of particle emissions were characterized for PLA-based printing emissions and found to vary depending on the filament employed. This is the first 3D printing study employing WIBS for particulate characterization, and distinct sizes and shape profiles that differ from other ambient WIBS studies were observed. The findings emphasize the importance of implementing safety measures in all 3D printing environments, including the home, such as improved ventilation, thermoplastic material, and brand selection. Additionally, our research highlights the need for further regulatory guidelines to ensure the safe use of 3D printing technologies, particularly in the home setting

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