278 research outputs found

    Solar array electrical performance assessment for Space Station Freedom

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    Electrical power for Space Station Freedom will be generated by large Photovoltaic arrays with a beginning of life power requirement of 30.8 kW per array. The solar arrays will operate in a Low Earth Orbit (LEO) over a design life of fifteen years. This paper provides an analysis of the predicted solar array electrical performance over the design life and presents a summary of supporting analysis and test data for the assigned model parameters and performance loss factors. Each model parameter and loss factor is assessed based upon program requirements, component analysis, and test data to date. A description of the LMSC performance model, future test plans, and predicted performance ranges are also given

    An Economic Analysis of Texas Shrimp Season Closures

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    Management of the Texas penaeid shrimp fishery is aimed at increasing revenue from brown shrimp, Penaeus aztecus, landings and decreasing the level of discards. Since 1960 Texas has closed its territorial sea for 45-60 days during peak migration of brown shrimp to the Gulf of Mexico. In 1981 the closure was extended to 200 miles to include the U.S. Exclusive Economic Zone. Simulation modeling is used in this paper to estimate the changes in landings, revenue, costs, and economic rent attributable to the Texas closure. Four additional analyses were conducted to estimate the effects of closing the Gulf 1- to 4-fathom zone for 45 and 60 days, with and without effort redirected to inshore waters. Distributional impacts are analyzed in terms of costs, revenues, and rents, by vessel class, shrimp species, vessel owner, and crew

    Development of a Florida Seafood Program Using a Multi-Disciplinary Team

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    The seafood industry in Florida is complex, with more than 80 varieties of Florida seafood commodities and an increasing number of imported products. This variety increases consumer confusion, especially with the growing concern about the origin, sustainability, and safety of seafood products. The objective of the Florida Seafood At Your Fingertips program is to provide Florida Extension agents with updated, science-based information regarding seafood, which will result in increased consumer awareness and consumption. Combining a survey instrument, curriculum modules, public displays, and a mobile application with the teaching expertise of Extension has allowed this program to reach consumers throughout Florida

    Molecular investigation of Keap1-dependent regulation of the Nrf2 cell defence pathway

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    Mammalian cells have evolved highly regulated defence pathways, which are activated in response to stress. The transcription factor Nrf2 is activated in response to chemical and oxidative stress and induces the expression of antioxidants and detoxification enzymes. Nrf2 activity is regulated by its cysteine-rich repressor protein Keap1, which facilitates Nrf2 degradation. In the presence of electrophilic compounds and/or oxidative stress, Keap1-mediated repression of Nrf2 is hindered, allowing the nuclear localisation of Nrf2 and the up-regulation of cell defence gene expression. The dysregulation of the Nrf2 pathway has been associated with many disease pathologies, and is a promising therapeutic target. Furthering our understanding of the chemico-biological triggers for Nrf2 activation may inform the design of novel Nrf2-inducers with increased efficacy and reduced toxicity. The modification of one or more cysteine residues in Keap1 by electrophiles is believed to be central to Nrf2 activation. Therefore, the aims of the studies in this thesis were to investigate the chemical modification of Keap1 cysteine residues by Nrf2-inducers and identify novel Keap1 binding proteins, which may play a role in the regulation of Nrf2 activity. Previous work carried out in this lab identified cysteine residues in Keap1 that are covalently modified by a panel of Nrf2-inducing compounds in recombinant Keap1 protein and in cells. Additionally, Nrf2 can be induced by glutathione (GSH) depletion in the absence of Keap1 adduct formation. We hypothesised that GSH depletion permits reactive oxygen species (ROS) to accumulate and oxidise Keap1 cysteine residues, thereby inducing Nrf2. To address this, we treated Keap1-V5 expressing HEK293T cells with Nrf2-inducing compounds. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to investigate the ability of these compounds to form adducts with Keap1 cysteine residues, or induce reversible/irreversible redox modifications of these residues. We show that compounds which form covalent adducts with Keap1 and deplete GSH (i.e. 2,4-dinitrochlorobenzene) or do not deplete GSH (i.e. dexamethasone 2,1-mesylate) induce modifications of Keap1 that could be representative of oxidation. However compounds which do not form covalent adducts with Keap1 but cause oxidative stress (i.e. hydrogen peroxide), or GSH depletion (i.e. L-buthionine-sulfoximine), do not appear to cause oxidative-like modification of Keap1 cysteines. We therefore show that some Nrf2 inducers promote the formation of reversible and/or irreversible redox modifications of Keap1 which could be due to thiol oxidation, although this is not dependent on GSH depletion. To further explore the modification of Keap1 cysteine residues by Nrf2 inducers, we investigated the ability of triterpenoids (TPs) to modify Keap1. TPs, in particular methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate (CDDO-Me), are potent inducers of Nrf2 and are potential therapeutic agents. However, the mechanism of Nrf2 activation by TPs has not been fully elucidated using LC-MS/MS. We identify key cysteine residues in Keap1 which are adducted by a chemically-tuned TP (CDDO-Epoxide) in recombinant Keap1 and in cells expressing Keap1-V5. Additionally, we use an in silico modelling approach to visualise the binding orientations of CDDO-Epoxide with key Keap1 cysteine residues. Correlating the potency of a panel of TPs towards the Nrf2 pathway with their in silico propensity to bind covalently to the identified residues showed no relationship. However, we show significant positive correlation between the potency of these TPs towards Nrf2 and their in silico propensity to bind non-covalently in two cysteine-containing pockets (Cys-273, -288) in Keap1. These data reveal the specific sites of interactions between potent TP Nrf2 inducers and Keap1, and highlight the non-covalent binding of Keap1 by electrophiles as a potential mechanism of Nrf2 activation. The function of Keap1 is regulated by interactions with binding partners, such as sequestosome1 (p62) which targets it for autophagic degradation, or PGAM5 which localises Keap1 to the mitochondria. We previously used an LC-MS/MS approach to identify p62 as a novel Keap1-binding partner in cells. Therefore, we reasoned that using the same experimental approach with a more sensitive MS system, we could identify additional Keap1-binding proteins. Specifically, we identified a large number of proteins that co-purified with Keap1-V5 from HEK293T cell lysates, of which 55 were found to contain a known Keap1 binding motif, such as the one found in Nrf2, p62 and PGAM5. Network analysis highlighted the potential link between Keap1/Nrf2 and the p53 cell survival pathway. We validated the LC-MS/MS data using a yeast 2-hybrid screen, which reveals HBS1L, RIC8A and PSMD3 as novel Keap1 binding partners, although the functional relevance of the interaction of these proteins with Keap1 requires further investigation. In summary, the data presented in this thesis demonstrates that whilst the covalent modification of Keap1 cysteines is an important aspect of Nrf2 induction, the oxidation of Keap1 thiols may be an alternative mechanism. We identify key cysteine residues in Keap1 covalently modified by a potent TP Nrf2 inducer in recombinant protein and cells, but show that non-covalent modification of Keap1 may be involved in the process of Nrf2 activation by this class of compound. It will be important in future studies to determine how the modification of Keap1 cysteine residues is translated to the activation of Nrf2. Additionally, we identify putative novel Keap1 binding partners which may serve to regulate the activity of the Nrf2 pathway. Overall, these findings expand our understanding of the chemical and molecular interactions that govern the activity of Nrf2, and will therefore contribute to the ongoing efforts to target this pathway as a novel therapeutic strategy in numerous diseases

    Generalized Alder-Type Partition Inequalities

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    In 2020, Kang and Park conjectured a "level 22" Alder-type partition inequality which encompasses the second Rogers-Ramanujan Identity. Duncan, Khunger, the fourth author, and Tamura proved Kang and Park's conjecture for all but finitely many cases utilizing a "shift" inequality and conjectured a further, weaker generalization that would extend both Alder's (now proven) as well as Kang and Park's conjecture to general level. Utilizing a modified shift inequality, Inagaki and Tamura have recently proven that the Kang and Park conjecture holds for level 33 in all but finitely many cases. They further conjectured a stronger shift inequality which would imply a general level result for all but finitely many cases. Here, we prove their conjecture for large enough nn, generalize the result for an arbitrary shift, and discuss the implications for Alder-type partition inequalities

    Ohio Housing Needs Assessment

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    X Chromosome Inactivation and Xist Evolution in a Rodent Lacking LINE-1 Activity

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    Dosage compensation in eutherian mammals occurs by inactivation of one X chromosome in females. Silencing of that X chromosome is initiated by Xist, a large non-coding RNA, whose coating of the chromosome extends in cis from the X inactivation center. LINE-1 (L1) retrotransposons have been implicated as possible players for propagation of the Xist signal, but it has remained unclear whether they are essential components. We previously identified a group of South American rodents in which L1 retrotransposition ceased over 8 million years ago and have now determined that at least one species of these rodents, Oryzomys palustris, still retains X inactivation. We have also isolated and analyzed the majority of the Xist RNA from O. palustris and a sister species retaining L1 activity, Sigmodon hispidus, to determine if evolution in these sequences has left signatures that might suggest a critical role for L1 elements in Xist function. Comparison of rates of Xist evolution in the two species fails to support L1 involvement, although other explanations are possible. Similarly, comparison of known repeats and potential RNA secondary structures reveals no major differences with the exception of a new repeat in O. palustris that has potential to form new secondary structures

    Project E3 (E-Filter, E-Frame, E-Page)

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    E-Filter: Our E-flow air filtration system is designed solely from ewaste materials. It uses solar e-wastes to generate power and purifies the air from smoke, odor, toxins & dust by passing it through several designed filters. E-page: Check our e-wasterecycling ideas website (http://e-waste-recycle-idea.blogspot.com/) Use these simple ideas to use your old electronics, enjoy creating your new stuff by yourself, feel green and share your new ideas with others. E-Frame: We designed an eframe; a digital photo frame which displays photographs and movies in high resolution with voice.Ope

    FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs

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    Focal adhesion kinase (FAK) localizes to focal adhesions and is overexpressed in many cancers. FAK can also translocate to the nucleus, where it binds to, and regulates, several transcription factors, including MBD2, p53 and IL-33, to control gene expression by unknown mechanisms. We have used ATAC-seq to reveal that FAK controls chromatin accessibility at a subset of regulated genes. Integration of ATAC-seq and RNA-seq data showed that FAK-dependent chromatin accessibility is linked to differential gene expression, including of the FAK-regulated cytokine and transcriptional regulator interleukin-33 (Il33), which controls anti-tumor immunity. Analysis of the accessibility peaks on the Il33 gene promoter/enhancer regions revealed sequences for several transcription factors, including ETS and AP-1 motifs, and we show that c-Jun, a component of AP-1, regulates Il33 gene expression by binding to its enhancer in a FAK kinase-dependent manner. This work provides the first demonstration that FAK controls transcription via chromatin accessibility, identifying a novel mechanism by which nuclear FAK regulates biologically important gene expression

    Evidence for Pleistocene gene flow through the ice-free corridor from extinct horses and camels from Natural Trap Cave, Wyoming

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    Natural Trap Cave (Bighorn Mountains, Wyoming) preserves an abundance of fossil remains from extinct Late Pleistocene fauna and is situated near a past migration route that likely connected populations in Eastern Beringia and the contiguous US—the ice-free corridor between the Cordilleran and Laurentide icesheets. Some palaeontological evidence supports a correspondingly high affinity between fauna recorded in Natural Trap Cave and Eastern Beringia versus elsewhere in the contiguous US, but this hypothesis has not yet been extensively tested using genetic data. In the present study, we analysed 16 horse specimens and one camel specimen from Natural Trap Cave. Of the horse specimens we analysed, we obtained 10 unique and previously unreported mitochondrial haplotypes belonging to two distinct (extinct) genetic clades—two haplotypes corresponded to a caballine horse (Equus sp.) and eight corresponded to the stilt-legged horse (Haringtonhippus francisci). With only one exception, it appears these newly sequenced individuals all shared a common ancestor more recently with Eastern Beringian individuals than with others from the contiguous US. In addition, mitochondrial data from a specimen assigned to Camelops sp. revealed that it shares a closer affinity with specimens from the Yukon Territory than those from Idaho or Nevada, though all appear to belong to a single species (“yesterday''s camel”; Camelops cf. hesternus). Together, these results are consistent with a high level of genetic connectivity between horse and camel populations in the Bighorn Mountains and Eastern Beringia during the Pleistocene. © 2021 Elsevier Ltd and INQU
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