89 research outputs found

    The synthesis of galectin-3-targeted cancer imaging agents

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    Galectin-3 is an animal lectin that recognises and binds to β-galactosides in glycoconjugates and is frequently over-expressed in cancerous states, potentially allowing inhibitors to serve as vector tags for targeted image contrast agents to give enhanced MRI and flourescence images. Derivatives of lactosamine with 3'-arylamides have been shown to be excellent inhibitors of galectin-3: 3'-naphthamide derivatives of lactosamine have previously been shown to bind to galectin-3 with kd_d<1 μM, and form the basis of the target imaging agent, which will also incorporate a spacer unit and a probe molecule. Problems with the reduction/acylation of an azide in a key disaccharide intermediate could not be resolved by alterations in the reaction conditions; incorporation of the required amide earlier in the synthesis failed to lead to disaccharide products. Employing a phthalimide as nitrogen protecting group has successfully produced a glycosyl donor precursor that will only require ring opening rather than the troublesome reduction/acylation. Using a propargyl group to protect the anomeric position in the glysosyl acceptor has allowed for the attachment of the linker via a click reaction and subsequent deprotection reactions and FITC installation has produced one of the compounds required for comparison studies

    Utilizing "Omic" technologies to identify and prioritize novel sources of resistance to the oomycete pathogen <i>Phytophthora infestans</i> in potato germplasm collections

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    The biggest threat to potato production world-wide is late blight, caused by the oomycete pathogen Phytophthora infestans. A screen of 126 wild diploid Solanum accessions from the Commonwealth Potato Collection (CPC) with P. infestans isolates belonging to the genotype 13-A2 identified resistances in the species S. bulbocastanum, S. capsicibaccatum, S. microdontum, S. mochiquense, S. okadae, S. pinnatisectum, S. polyadenium, S. tarijense and S. verrucosum. Effector-omics, allele mining and diagnostic RenSeq (dRenSeq) were utilized to investigate the nature of resistances in S. okadae accessions. dRenSeq in resistant S. okadae accessions 7129, 7625, 3762 and a bulk of 20 resistant progeny confirmed the presence of full-length Rpi-vnt1.1 under stringent mapping conditions and corroborated allele mining results in the accessions 7129 and 7625 as well as Avr-vnt1 recognition in transient expression assays. In contrast, susceptible S. okadae accession 3761 and a bulk of 20 susceptible progeny lacked sequence homology in the 5’ end compared to the functional Rpi-vnt1.1 gene. Further evaluation of S. okadae accessions with late blight isolates that have a broad spectrum of virulence demonstrated that, although S. okadae accessions 7129, 7625 and 7629 contain functional Rpi-vnt1.1, they also carry a novel resistance gene. We provide evidence that existing germplasm collection are important sources of novel resistances and that ‘omic’ technologies such as dRenSeq-based genomics and effector-omics are efficacious tools to rapidly explore the diversity within these collections

    Physics Opportunities with the 12 GeV Upgrade at Jefferson Lab

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    This white paper summarizes the scientific opportunities for utilization of the upgraded 12 GeV Continuous Electron Beam Accelerator Facility (CEBAF) and associated experimental equipment at Jefferson Lab. It is based on the 52 proposals recommended for approval by the Jefferson Lab Program Advisory Committee.The upgraded facility will enable a new experimental program with substantial discovery potential to address important topics in nuclear, hadronic, and electroweak physics.Comment: 64 page

    Action to protect the independence and integrity of global health research

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    Storeng KT, Abimbola S, Balabanova D, et al. Action to protect the independence and integrity of global health research. BMJ GLOBAL HEALTH. 2019;4(3): e001746

    Avant-garde and experimental music

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    Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study

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    Objective To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection. Methods Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant. Results Between April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3–1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2. Conclusions Infection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians’ threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection

    Green tycoon : A mobile application game to introduce biorefining principles in green chemistry

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    Green Tycoon is a free-of-charge game-based mobile application that embraces a systems thinking approach to introducing students to a biorefining process model within green chemistry. Players adopt the role of a manager in a chemical factory, synthesizing the fictional compound, Yorkanone. Through upgrading the system and engaging with the integrated quiz, players can learn fundamental green chemistry principles while appreciating some of the considerations in biorefining. Green Tycoon was implemented with 33 undergraduate students where survey feedback demonstrated that the game was engaging and innovative and was a helpful tool to appreciate the importance of green chemistry when designing chemical processes. On the basis of pretest and post-test questions to evaluate learning gain, Green Tycoon proved to be a useful resource to introduce students to green chemistry and its role in moving toward a bioeconomy. Design of the mobile application serves as a useful example of what an upper-division undergraduate student with no coding knowledge can achieve through a chemistry education research project
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