1,085 research outputs found
Seated Portrait of Abraham Lincoln
Seated portrait of A. Lincoln by Alexander Gardner. BM; Published by E. Anthony...From Photographic Negative from Brady\u27s...https://scholarsjunction.msstate.edu/fvw-cdv/1584/thumbnail.jp
Seated Portrait of Abraham Lincoln
The CDV features a seated portrait of Abraham Lincoln taken by Alexander Gardner around 24 February 1861. Negative from Brady\u27s National Portrait Gallery. [Ref: O-53.]https://scholarsjunction.msstate.edu/fvw-cdv/1257/thumbnail.jp
Nitric oxide synthase 2A (NOS2A) polymorphisms are not associated with invasive pneumococcal disease
<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>(pneumococcus) is responsible for over one million deaths per year, with young children, the elderly and immunocompromised individuals being most at risk. Approximately half of East African children have been reported to be asymptomatic carriers of pneumococcus with invasive infection occurring after the disruption of the respiratory membrane which is believed to be caused by the host immune response. Racial incidence of invasive pneumococcal disease (IPD) is higher in certain populations even after adjusting for environmental factors suggesting a genetic component to disease susceptibility. The nitric oxide synthase 2A (NOS2A) gene is responsible for the production of nitric oxide under pathological conditions including host defence against bacterial infection. Nitric oxide is a modulator of apoptotic and inflammatory cascades and endothelial permeability. We hypothesised that genetic variants within this gene may predispose to disease risk and survival.</p> <p>Methods</p> <p>A cohort of 299 children with IPD (221 meningitis, 41 pneumonia and 37 with bacteraemia) and 931 age matched controls from Malawi were used in this study. We investigated nine haplotype tagging single nucleotide polymorphisms within the NOS2A gene and compared the presence or absence of the minor alleles in cases and controls and survivors and non-survivors within the cases.</p> <p>Results</p> <p>We observed no significant associations between cases and controls or with survival in either all IPD cases or in the separate analysis of meningitis cases. A near significant association was obtained for the comparison of rs8078340 in cases and controls (p-value, 0.078). However, results were unadjusted for multiple testing.</p> <p>Conclusion</p> <p>Our results suggest that polymorphic variation within the NOS2A gene does not influence invasive pneumococcal disease susceptibility or survival.</p
α-Synuclein aggregation inhibitory activity of the bromotyrosine derivatives aerothionin and aerophobin-2 from the subtropical marine sponge Aplysinella sp
The neuronal protein α-synuclein (α-syn) is one of the main constituents of intracellular amyloid aggregations found in the post-mortem brains of Parkinson’s disease (PD) patients. Recently, we screened the MEOH extracts obtained from 300 sub-tropical marine invertebrates for α-syn binding activity using affinity MS and this resulted in the extract of the Verongida marine sponge Aplysinella sp. 1194, (QM G339263) displaying molecules that bind to the protein. The subsequent bioassay-guided separation of the Aplysinella sp. extract led to the isolation of the known bromotyrosine derivatives (+)-aerothionin (1) and (+)-aerophobin-2 (2). Both compounds bind to α-syn as detected by a MS affinity assay and inhibit α-syn aggregation in an assay that uses the fluorescence probe, thioflavin T, to detect aggregation. (+)-Aerothionin (1) was toxic to primary dopaminergic neurons at its expected α-syn aggregation inhibitory concentration and so could not be tested for pSyn aggregates in this functional assay. (+)-Aerophobin-2 (2) was not toxic and shown to weakly inhibit pSyn aggregation in primary dopaminergic neurons at 10 µM.Peer reviewe
Hesperine, a new imidazole alkaloid and α-synuclein binding activity of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine from the marine sponge Clathria (Thalysias) cf. hesperia
During a high-throughput screen of 300 Australian marine invertebrate extracts, the extract of the marine sponge Clathria (Thalysias) cf. hesperia was identified with α-synuclein binding activity. The bioassay-guided purification of this extract resulted in the isolation of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine (2) as the α-syn binder along with one new compound, hesperine (1), and five known compounds, indole-3-carboxaldehyde (3), (Z)-2'-demethylaplysinopsin (4), 2-amino-4'-hydroxyacetophenone (5), 4-hydroxybenzoic acid (6) and 4-hydroxybenzaldehyde (7). Herein, we report the structure elucidation of hesperine (1) and α-syn binding activity of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine (2).Peer reviewe
α-Synuclein Aggregation Inhibitory Prunolides and a Dibrominated β-Carboline Sulfamate from the Ascidian Synoicum prunum
Seven new polyaromatic bis-spiroketal-containing butenolides, the prunolides D–I (4–9) and cis-prunolide C (10), a new dibrominated β-carboline sulfamate named pityriacitrin C (11), alongside the known prunolides A–C (1–3) were isolated from the Australian colonial ascidian Synoicum prunum. The prunolides D–G (4–7) represent the first asymmetrically brominated prunolides, while cis-prunolide C (10) is the first reported with a cis-configuration about the prunolide’s bis-spiroketal core. The prunolides displayed binding activities with the Parkinson’s disease-implicated amyloid protein α-synuclein in a mass spectrometry binding assay, while the prunolides (1–5 and 10) were found to significantly inhibit the aggregation (>89.0%) of α-synuclein in a ThT amyloid dye assay. The prunolides A–C (1–3) were also tested for inhibition of pSyn aggregate formation in a primary embryonic mouse midbrain dopamine neuron model with prunolide B (2) displaying statistically significant inhibitory activity at 0.5 μM. The antiplasmodial and antibacterial activities of the isolates were also examined with prunolide C (3) displaying only weak activity against the 3D7 parasite strain of Plasmodium falciparum. Our findings reported herein suggest that the prunolides could provide a novel scaffold for the exploration of future therapeutics aimed at inhibiting amyloid protein aggregation and the treatment of numerous neurodegenerative diseases.Peer reviewe
Quantitative understanding of negative thermal expansion in scandium trifluoride from neutron total scattering measurements
Negative thermal expansion (NTE) - the phenomenon where some materials shrink
rather than expand when heated - is both intriguing and useful, but remains
poorly understood. Current understanding hinges on the role of specific
vibrational modes, but in fact thermal expansion is a weighted sum of
contributions from every possible mode. Here we overcome this difficulty by
deriving a real-space model of atomic motion in the prototypical NTE material
scandium trifluoride, ScF3, from total neutron scattering data. We show that
NTE in this material depends not only on rigid unit modes - the vibrations in
which the scandium coordination octahedra remain undistorted - but also on
modes that distort these octahedra. Furthermore, in contrast with previous
predictions, we show that the quasiharmonic approximation coupled with
renormalisation through anharmonic interactions describes this behaviour well.
Our results point the way towards a new understanding of how NTE is manifested
in real materials.Comment: 13 pages, 6 figures; version
Solution-Printed Organic Semiconductor Blends Exhibiting Transport Properties on Par with Single Crystals
Solution-printed organic semiconductors have emerged in recent years as promising contenders for roll-to-roll manufacturing of electronic and optoelectronic circuits. The stringent performance requirements for organic thin-film transistors (OTFTs) in terms of carrier mobility, switching speed, turn-on voltage and uniformity over large areas require performance currently achieved by organic single-crystal devices, but these suffer from scale-up challenges. Here we present a new method based on blade coating of a blend of conjugated small molecules and amorphous insulating polymers to produce OTFTs with consistently excellent performance characteristics (carrier mobility as high as 6.7 cm2V−1s−1, low threshold voltages of \u3c1V and low sub threshold swings \u3c0.5Vdec−1). Our findings demonstrate that careful control over phase separation and crystallization can yield solution-printed polycrystalline organic semiconductor films with transport properties and other figures of merit on par with their single-crystal counterparts
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Lead candidates for high-performance organic photovoltaics from high-throughput quantum chemistry – the Harvard Clean Energy Project
The virtual high-throughput screening framework of the Harvard Clean Energy Project allows for the computational assessment of candidate structures for organic electronic materials – in particular photovoltaics – at an unprecedented scale. We report the most promising compounds that have emerged after studying 2.3 million molecular motifs by means of 150 million density functional theory calculations. Our top candidates are analyzed with respect to their structural makeup in order to identify important building blocks and extract design rules for efficient materials. An online database of the results is made available to the community.Engineering and Applied Science
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