2,776 research outputs found

    Development of novel antimalarials targeting the plasmodial lactate transporter (PfFNT) through a fluorescence cross-correlation spectroscopy-based approach and functional assay

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    Drug resistance is a significant obstacle in the fight against malaria, prompting the exploration of new treatment approaches and drug targets. One potential target is the recently discovered plasmodial lactate transporter, PfFNT (short for Plasmodium falciparum formate-nitrite transporter). Several studies have shown that inhibiting this transporter can cause the accumulation of toxic levels of lactate within the parasite, leading to its death. Two compounds, BH296 and BH267.meta, have been developed to target both the PfFNT wild type (wt) and a relevant mutant, G107S. So far, these compounds have only been tested using a yeast-based functional assay, and biophysical characterization was missing. In this study, fluorescence cross-correlation spectroscopy (FCCS) measurements were performed to determine true Ki-values, as well as kon and koff rate constants for the binding of inhibitors to both the PfFNT wt and G107S mutant. Once the reliability of FCCS measurements had been confirmed, a compound library of 2,000 inhibitors was screened to identify novel scaffolds that have the potential to inhibit PfFNT. FCCS only allows the search for new inhibitors that displace the existing inhibitor, i.e., share the same binding pocket. To identify an alternative binding site, a functional screening assay with AZD3965 and Metformin was developed in this thesis

    Modern meat: the next generation of meat from cells

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    Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

    Digital agriculture: research, development and innovation in production chains.

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    Digital transformation in the field towards sustainable and smart agriculture. Digital agriculture: definitions and technologies. Agroenvironmental modeling and the digital transformation of agriculture. Geotechnologies in digital agriculture. Scientific computing in agriculture. Computer vision applied to agriculture. Technologies developed in precision agriculture. Information engineering: contributions to digital agriculture. DIPN: a dictionary of the internal proteins nanoenvironments and their potential for transformation into agricultural assets. Applications of bioinformatics in agriculture. Genomics applied to climate change: biotechnology for digital agriculture. Innovation ecosystem in agriculture: Embrapa?s evolution and contributions. The law related to the digitization of agriculture. Innovating communication in the age of digital agriculture. Driving forces for Brazilian agriculture in the next decade: implications for digital agriculture. Challenges, trends and opportunities in digital agriculture in Brazil

    2023 GREAT Day Program

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    SUNY Geneseo’s Seventeenth Annual GREAT Day. Geneseo Recognizing Excellence, Achievement & Talent Day is a college-wide symposium celebrating the creative and scholarly endeavors of our students. http://www.geneseo.edu/great_dayhttps://knightscholar.geneseo.edu/program-2007/1017/thumbnail.jp

    Combining Metabolic Engineering and Synthetic Biology Approaches for the Production of Abscisic Acid in Yeast

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    Nature presents us with a myriad of complex and diverse molecules. Many of these molecules prove to be useful to humans and find applications as pharmaceuticals, biofuels, agrochemicals, cosmetic ingredients or food additives. One highly promising natural product with a broad range of potential applications is the terpenoid abscisic acid (ABA). ABA fulfils a pivotal role in higher plants by regulating various developmental processes as well as abiotic stress responses. However, ABA is also produced in many other organisms, including humans. It appears to be a ubiquitous and evolutionary conserved signalling molecule throughout nature. Genetically engineered microorganisms, referred to as microbial cell factories, can be a sustainable source of natural products. In this thesis, a cell factory for the heterologous production of ABA was established and optimized employing the yeast Saccharomyces cerevisiae. Cell factory development is an inherently time-consuming process. As an enabling technology for subsequent work on the ABA cell factory, we expanded the modular cloning toolkit for yeast and made it more applicable for common genetic engineering tasks (Paper I). The ABA biosynthetic pathway of Botrytis cinerea was used to construct an ABA-producing S. cerevisiae strain (Paper II). The activity of two B. cinerea proteins, BcABA1 and BcABA2, was found to limit ABA titers. Two optimization approaches were devised for the following studies. Firstly, various rational engineering targets were explored, of which the native yeast gene PAH1 was identified as the most promising candidate (Paper III). Knockdown of PAH1 benefited ABA production without affecting growth. Secondly, platform strains for screening BcABA1 and BcABA2 enzyme libraries were developed, which utilize an ABA biosensor and enable a high throughput screening approach (Paper IV). In this work, we combined metabolic engineering and synthetic biology approaches for the heterologous production of ABA, and furthermore provided tools and insights that will be useful beyond the scope of this project

    Voicing Kinship with Machines: Diffractive Empathetic Listening to Synthetic Voices in Performance.

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    This thesis contributes to the field of voice studies by analyzing the design and production of synthetic voices in performance. The work explores six case studies, consisting of different performative experiences of the last decade (2010- 2020) that featured synthetic voice design. It focusses on the political and social impact of synthetic voices, starting from yet challenging the concepts of voice in the machine and voice of the machine. The synthetic voices explored are often playing the role of simulated artificial intelligences, therefore this thesis expands its questions towards technology at large. The analysis of the case studies follows new materialist and posthumanist premises, yet it tries to confute the patriarchal and neoliberal approach towards technological development through feminist and de-colonial approaches, developing a taxonomy for synthetic voices in performance. Chapter 1 introduces terms and explains the taxonomy. Chapter 2 looks at familiar representations of fictional AI. Chapter 3 introduces headphone theatre exploring immersive practices. Chapters 4 and 5 engage with chatbots. Chapter 6 goes in depth exploring Human and Artificial Intelligence interaction, whereas chapter 7 moves slightly towards music production and live art. The body of the thesis includes the work of Pipeline Theatre, Rimini Protokoll, Annie Dorsen, Begüm Erciyas, and Holly Herndon. The analysis is informed by posthumanism, feminism, and performance studies, starting from my own practice as sound designer and singer, looking at aesthetics of reproduction, audience engagement, and voice composition. This thesis has been designed to inspire and provoke practitioners and scholars to explore synthetic voices further, question predominant biases of binarism and acknowledge their importance in redefining technology

    In vitro-undersøkelser av infeksjoner med bovintkoronavirus og Cryptosporidium parvum

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    Intestinal infection causing diarrhoea is a major health problem among calves accounting for about 40% of calf diseases in Norway. Calves are especially susceptible to gastroenteritis during the first month of life of which bovine coronavirus (BCoV) and the intracellular parasite Cryptosporidium parvum (C. parvum) are the two major enteropathogens involved. Several studies have indicated that mixed infections are more common among diarrhoeal calves and that co-infections are associated with greater symptom severity. However, the pathogen-pathogen interplay and host-pathogen interaction during co-infection are unknown. Therefore, the overall objective of this thesis was to study the interplay between BCoV and C. parvum during infection and their possible effects on the host using in vitro models. To study the BCoV and C. parvum interactions during infection, human HCT-8 cells were sequentially and simultaneously inoculated with the two pathogens. Quantitative results from (RT)-qPCR revealed prior inoculation of cells with one pathogen did not have any effect on replication of the other. Co-inoculation, however, showed an interesting result indicating binding of BCoV to C. parvum sporozoites. There was an increase in viral RNA in presence of sporozoites at 1 hpi (hours post inoculation) which was no longer evident at 24 hpi indicating entrapment of virus in the parasitophorous vacuole. To test whether the attachment between BCoV and C. parvum sporozoites could be specific, bovine norovirus (naked) and equine herpes virus-1 (enveloped), were included in the study. The results indicated no binding between sporozoites and these viruses, which strengthens our assumption that binding of BCoV to the sporozoites is specific. Furthermore, flow cytometry to study the proportion of single and co-infected cells at 72 hpi showed that C. parvum and BCoV infected 1-11% and 10-20% of the HCT-8 cells, respectively, with only 0.04% of double infected cells. The host response was investigated with RNASeq of HCT-8 cells inoculated with BCoV alone, C. parvum alone, and BCoV/C. parvum simultaneously. There were more than 6000 differentially expressed genes (DEGs) in BCoV- and co-infected cells while only 52 DEGs were found for C. parvum infection at 72 hpi. Pathway (KEGG) and gene ontology (GO) analysis of BCoV- and co-infected cells revealed involvement of mostly immune related pathways (NF-κB, TNF or, IL-17), apoptosis, and regulation of transcription while limited effect was exerted by C. parvum under our experimental settings. The most enriched GO terms from C. parvum-infected cells at 24 hpi belonged to metabolic categories but at 72 hpi additional GO terms, such as cell death and responses to oxygen-containing compounds, occurred. Despite the modulation observed in the co-infection being dominated by the virus, which was probably due to differences in the infection rate of the pathogens, over 800 DEGs were exclusively expressed in co-infected cells at 72 hpi. Our findings provide insights on possible biomarkers associated with co-infection, which could be further explored in vivo. Furthermore, a 3D bovine enteroid model (complex model due to heterogenous cell population) was established as a replication system for BCoV. Immunostaining showed that the enteroids had a differentiated cell population. RT-qPCR results of the infected enteroids showed seven-fold increase in BCoV RNA at 72 hpi. The BCoV S-protein was detected by immunostaining, which indicates that virus particles might be produced. The expression of selected genes during BCoV infection of the enteroids was compared with the expression we previously found in HCT-8 cells. The pro-inflammatory responses of the enteroids such as IL-8 and IL-1A were comparable in the two models, while the expression of CXCL-3, MMP13, and TNF-α was significantly downregulated in the enteroids. In conclusion, there was a limited impact of co-infections on replication of the two agents, but upon co-inoculation we found binding of BCoV to the sporozoites which inhibited viral replication. The host transcriptome study revealed that some of the genes exclusively expressed during co-infection could be suggestive of possible biomarkers of co-infections, and their role in the pathogenesis of these intestinal infections should be addressed using in vitro models (such as bovine enteroids) and in vivo. Bovine enteroids were able to support the replication of BCoV but need to be further explored for C. parvum infection. Comparative gene expression studies of enteroids and live animals are necessary to clarify whether the in vitro model represents a good alternative to replace in vivo experiments

    2023-2024 Undergraduate Catalog

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    2023-2024 undergraduate catalog for Morehead State University

    Abstract Book

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    Proceedings of APP 11th ANNUAL CONVENTION AND 5th INDO SWISS CONFERENCE 16 – 17, DEC-2022 &nbsp
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