689 research outputs found
Consideration for high accuracy radiation efficiency measurements for the Solar Power Satellite (SPS) subarrays
The transmit beam and radiation efficiency for 10 metersquare subarray panels were quantified. Measurement performance potential of far field elevated and ground reflection ranges and near field technique were evaluated. The state-of-the-art of critical components and/or unique facilities required was identified. Relative cost, complexity and performance tradeoffs were performed for techniques capable of achieving accuracy objectives. It is considered that because of the large electrical size of the SPS subarray panels and the requirement for high accuracy measurements, specialized measurement facilities are required. Most critical measurement error sources have been identified for both conventional far field and near field techniques. Although the adopted error budget requires advances in state-of-the-art of microwave instrumentation, the requirements appear feasible based on extrapolation from today's technology. Additional performance and cost tradeoffs need to be completed before the choice of the preferred measurement technique is finalized
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Strategic verbal rehearsal in adolescents with mild intellectual disabilities: A multi-centre European study
Background: There is a long-held view that verbal short-term memory problems of individuals with intellectual disabilities (ID) might be due to a deficit in verbal rehearsal. However, the evidence is inconclusive and word length effects as indicator of rehearsal have been criticised.
Aim & Method: The aim of this multi-site European study was to investigate verbal rehearsal in adolescents with mild ID (n=90) and a comparison group of typically developing children matched individually for mental age (MA, n=90). The investigation involved: (1) a word length experiment with non-verbal recall using pointing and (2) ‘self-paced’ inspection times to infer whether verbal strategies were utilised when memorising a set of pictorial items.
Results: The word length effect on recall did not interact with group, suggesting that adolescents with ID and MA comparisons used similar verbal strategies, possibly phonological recoding of picture names. The inspection time data suggested that high span individuals in both groups used verbal labelling or single item rehearsal on more demanding lists, as long named items had longer inspection times.
Conclusions: The findings suggest that verbal strategy use is not specifically impaired in adolescents with mild ID and is mental age appropriate, supporting a developmental perspective
Personal Finance: An Interdisciplinary Profession
This commentary recommends that financial counseling and planning research, education, and practice be framed as an interdisciplinary profession called personal finance. Authors summarize the history of the profession and key theories providing the conceptual foundation. In order for the emerging profession of personal finance to achieve significant visibility and gain maturity, professionals must reach consensus on definining collective scholarship. Readers are encouraged to engage in the dialogue and comment on the call to action by contacting the lead author
Intimal smooth muscle cells are a source but not a sensor of anti-inflammatory CYP450 derived oxylipins
AbstractVascular pathologies are associated with changes in the presence and expression of morphologically distinct vascular smooth muscle cells. In particular, in complex human vascular lesions and models of disease in pigs and rodents, an intimal smooth muscle cell (iSMC) which exhibits a stable epithelioid or rhomboid phenotype in culture is often found to be present in high numbers, and may represent the reemergence of a distinct developmental vascular smooth muscle cell phenotype. The CYP450-oxylipin - soluble epoxide hydrolase (sEH) pathway is currently of great interest in targeting for cardiovascular disease. sEH inhibitors limit the development of hypertension, diabetes, atherosclerosis and aneurysm formation in animal models. We have investigated the expression of CYP450-oxylipin-sEH pathway enzymes and their metabolites in paired intimal (iSMC) and medial (mSMC) cells isolated from rat aorta. iSMC basally released significantly larger amounts of epoxy-oxylipin CYP450 products from eicosapentaenoic acid > docosahexaenoic acid > arachidonic acid > linoleic acid, and expressed higher levels of CYP2C12, CYP2B1, but not CYP2J mRNA compared to mSMC. When stimulated with the pro-inflammatory TLR4 ligand LPS, epoxy-oxylipin production did not change greatly in iSMC. In contrast, LPS induced epoxy-oxylipin products in mSMC and induced CYP2J4. iSMC and mSMC express sEH which metabolizes primary epoxy-oxylipins to their dihydroxy-counterparts. The sEH inhibitors TPPU or AUDA inhibited LPS-induced NFκB activation and iNOS induction in mSMC, but had no effect on NFκB nuclear localization or inducible nitric oxide synthase in iSMC; effects which were recapitulated in part by addition of authentic epoxy-oxylipins. iSMCs are a rich source but not a sensor of anti-inflammatory epoxy-oxylipins. Complex lesions that contain high levels of iSMCs may be more resistant to the protective effects of sEH inhibitors
Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism
Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor. [Image: see text
Synthesis of rearranged unsaturated drimane derivatives
A full account to the preparation and application of three appropriately substituted vinylcyclohexenes (2,2-dimethyl-3-vinylcyclohex-3-en-1-ol, 2,2-dimethyl-3-vinylcyclohex-3-en-1-one and 3,3-dimethyl-2-vinylcyclohexene) in thermal Diels-Alder reactions with alpha,beta-unsaturated esters (methyl tiglate and methyl angelate) is given. This approach delivered the racemic synthesis of ten octalin derivatives bearing a rearranged drimane skeleton (4 diastereomers of 1-methoxycarbonyl-6-hydroxy-1,2,5,5-tetramethyl-1,2,3,5,6,7, 8,8a-octahydronaphthalene; 1-methoxycarbonyl-6-oxo-1,2,5,5-tetramethyl-1,2,3,4,5,6,7,8-octahydronaphthalene; 2-methoxycarbonyl-6-oxo-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene; 3 diastereomers of 1-methoxycarbonyl-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene and 2-methoxycarbonyl-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene) . Central synthetic features included preparation of enoltriflates by Stang's protocol and the successful palladium-catalyzed cross-coupling reaction (Stille reaction) of the triflate with the tri-n-butylvinylstannane. The octalins relative stereochemistry was unequivocally ascertained by spectroscopic methods and/or X-ray crystallography and these data now stand as useful tools to support the correct assignment of related natural products usually isolated in minute amounts.O presente trabalho relata a preparação e aplicação de três vinilcicloexenos devidamente funcionalizados (2,2-dimetil-3-vinilcicloex-3-en-1-ol, 2,2-dimetil-3-vinilcicloex-3-en-1-ona e 3,3-dimetil-2-vinilcicloexeno) em reações de Diels-Alder com ésteres a,b-insaturados (tiglato de metila e angelato de metila). Esta abordagem levou à sÃntese racêmica de dez octalinas possuindo esqueleto drimânico rearranjado (4 diastereoisômeros do 1-metoxicarbonil-6-hidroxi-1,2,5,5-tetrametil-1,2,3,5,6,7,8,8a-octaidronaftaleno; 1-metoxicarbonil-6-oxo-1,2,5,5-tetrametil-1,2,3,4,5,6,7,8 -ocataidronaftaleno; 2-metoxicarbonil-6-oxo-1,2,5,5-tetrametil-1,2,3,5,6,7, 8,8a-octaidronaftaleno; 3 diastereoisômeros do 1-metoxicarbonil-1,2,5,5-tetrametil-1,2,3,5,6,7,8,8a-octaidronaftaleno e 2-metoxicarbonil-1,2,5,5-tetrametil-1,2,3,5,6,7,8,8a-octaidronaftaleno) . Para a preparação dos dienos, utilizou-se a reação de acoplamento catalisada por paládio (reação de Stille) entre enoltriflatos (preparados pelo protocolo de Stang) e tri-n-butilvinilestanana. A estereoquÃmica relativa dos produtos foi estabelecida a partir de métodos espectroscópicos e análise de difração de raios-X de alguns dos derivados. Estes dados podem servir para a identificação de novos produtos naturais e corrigir algumas estruturas da literatura.391402Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento CientÃfico e Tecnológico (CNPq
Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism
Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known
whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate
is partially converted to mesaconate intracellularly and that
mesaconate accumulation in macrophage activation depends
on prior itaconate synthesis. When added to human cells in
supraphysiological concentrations, all three isomers reduce
lactate levels, whereas itaconate is the strongest succinate
dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino
acid metabolism, modulate cytokine/chemokine release and
reduce interferon signalling, oxidative stress and the release
of viral particles. Of the three isomers, citraconate is the
strongest electrophile and nuclear factor-erythroid 2-related
factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of
itaconate by cis-aconitate decarboxylase (ACOD1), probably
by competitive binding to the substrate-binding site. These
results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate
as the first naturally occurring ACOD1 inhibitor
Quantum mechanical studies of lincosamides
Lincosamides are a class of antibiotics used both in clinical and veterinary practice for a wide range of pathogens. This group of drugs inhibits the activity of the bacterial ribosome by binding to the 23S RNA of the large ribosomal subunit and blocking protein synthesis. Currently, three X-ray structures of the ribosome in complex with clindamycin are available in the Protein Data Bank, which reveal that there are two distinct conformations of the pyrrolidinyl propyl group of the bound clindamycin. In this work, we used quantum mechanical methods to investigate the probable conformations of clindamycin in order to explain the two binding modes in the ribosomal 23S RNA. We studied three lincosamide antibiotics: clindamycin, lincomycin, and pirlimycin at the B3LYP level with the 6-31G** basis set. The focus of our work was to connect the conformational landscape and electron densities of the two clindamycin conformers found experimentally with their physicochemical properties. For both functional conformers, we applied natural bond orbital (NBO) analysis and the atoms in molecules (AIM) theory, and calculated the NMR parameters. Based on the results obtained, we were able to show that the structure with the intramolecular hydrogen bond C=O…H–O is the most stable conformer of clindamycin. The charge transfer between the pyrrolidine-derivative ring and the six-atom sugar (methylthiolincosamide), which are linked via an amide bond, was found to be the dominant factor influencing the high stability of this conformer
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