246 research outputs found
Voltammetric behaviour of drug molecules as a predictor of metabolic liabilities
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Electron transfer plays a vital role in drug metabolism and underlying toxicity mechanisms. Currently, pharmaceutical research relies on pharmacokinetics (PK) and absorption, distribution, metabolism, elimination and toxicity (ADMET) measurements to understand and predict drug reactions in the body. Metabolic stability (and toxicity) prediction in the early phases of the drug discovery and development process is key in identifying a suitable lead compound for optimisation. Voltammetric methods have the potential to overcome the significant barrier of new drug failure rates, by giving insight into phase I metabolism events which can have a direct bearing on the stability and toxicity of the parent drug being dosed. Herein, we report for the first time a data-mining investigation into the voltammetric behaviour of reported drug molecules and their correlation with metabolic stability (indirectly measured via t1/2), as a potential predictor of drug stability/toxicity in vivo. We observed an inverse relationship between oxidation potential and drug stability. Furthermore, we selected and prepared short-(2 h) drug molecules to prospectively survey the relationship between oxidation potential and stability
Imaging Oxygen Defects and their Motion at a Manganite Surface
Manganites are technologically important materials, used widely as solid
oxide fuel cell cathodes: they have also been shown to exhibit
electroresistance. Oxygen bulk diffusion and surface exchange processes are
critical for catalytic action, and numerous studies of manganites have linked
electroresistance to electrochemical oxygen migration. Direct imaging of
individual oxygen defects is needed to underpin understanding of these
important processes. It is not currently possible to collect the required
images in the bulk, but scanning tunnelling microscopy could provide such data
for surfaces. Here we show the first atomic resolution images of oxygen defects
at a manganite surface. Our experiments also reveal defect dynamics, including
oxygen adatom migration, vacancy-adatom recombination and adatom bistability.
Beyond providing an experimental basis for testing models describing the
microscopics of oxygen migration at transition metal oxide interfaces, our work
resolves the long-standing puzzle of why scanning tunnelling microscopy is more
challenging for layered manganites than for cuprates.Comment: 7 figure
Physiological and Environmental Requirements for Poplar (Populus deltoides) Bark Storage Protein Degradation
Supporting product distribution decisions of smallholder farmers
Smallholder farmers are usually very constrained in terms of market access, due to, among other factors, the low production volumes and subsequent lack of economies of scale, variable quality, difficulty in planning and unavailability of distribution channels. In some countries, alternative markets have emerged, in order to facilitate smallholder farmers’ access to markets. These can take the form of government feeding programs, that aim at providing an outlet for the smallholder farmer products, giving them priority in supplying public sector organisations. Such a program is the PNAE in Brazil, where local smallholder farmers can supply schools with raw materials for meals. This work aims to support smallholder farmers in distribution related decision-making. More specifically, it aims to allow farmers to maximise the profit from their participation in the government feeding programs through guiding them in the complex supply decision-making and product distribution planning processes. The paper presents the related method developed, as well as the results from a preliminary application of the method in a case study of a rural settlement in Brazil
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Effects of Irrigation Frequency and Nitrogen Fertilizer Rate on Water Stress, Nitrogen Uptake, and Plant Growth of Container-grown Rhododendron
The influence of irrigation frequency (same amount of water per day given at different times) and nitrogen (N) fertilizer rate on water stress [stomatal conductance (gs)], N uptake, and growth (biomass) of container-grown evergreen Rhododendron 'P.J.M. Compact' and 'English Roseum' and deciduous Rhododendron 'Gibraltar' was evaluated. Both N deficiency and high N rate increased water stress. Water stress was greatest in plants fertilized with the highest N rate and gs of plants grown with the higher N rates changed more in response to water deficits resulting from irrigation treatments and seasonal climatic changes. Watering plants more frequently decreased water stress of plants fertilized with higher N rates and altering irrigation frequency had little impact on alleviating water stress of N-deficient plants. Increasing irrigation frequency decreased N uptake efficiency (N uptake per gram N applied), increased N use efficiency (growth per gram N uptake) and altered biomass allocation with little influence on total plant biomass. Response of biomass allocation to N rates was similar among cultivars and response of biomass allocation to irrigation frequency varied among cultivars. Altering irrigation frequency changed either the availability of N in the growing substrate or the ability of roots to absorb N. Our results indicate that transitory increases in plant water stress can alter N uptake, N use, and plant form without detectable changes in total plant biomass.Keywords: P.J.M. compact,
Rhododendron 'Gibralter',
Rhododendron,
Nursery production,
Rhododendroon 'English Roseum',
Water use,
Nitrogen uptak
Atomic-scale visualization of initial growth of homoepitaxial SrTiO3 thin film on an atomically ordered substrate
The initial homoepitaxial growth of SrTiO3 on a (\surd13\times\surd13) -
R33.7{\deg}SrTiO3(001) substrate surface, which can be prepared under oxide
growth conditions, is atomically resolved by scanning tunneling microscopy. The
identical (\surd13\times\surd13) atomic structure is clearly visualized on the
deposited SrTiO3 film surface as well as on the substrate. This result
indicates the transfer of the topmost Ti-rich (\surd13\times\surd13) structure
to the film surface and atomic-scale coherent epitaxy at the film/substrate
interface. Such atomically ordered SrTiO3 substrates can be applied to the
fabrication of atom-by-atom controlled oxide epitaxial films and
heterostructures
Minimum Free Energy Path of Ligand-Induced Transition in Adenylate Kinase
Large-scale conformational changes in proteins involve barrier-crossing transitions on the complex free energy surfaces of high-dimensional space. Such rare events cannot be efficiently captured by conventional molecular dynamics simulations. Here we show that, by combining the on-the-fly string method and the multi-state Bennett acceptance ratio (MBAR) method, the free energy profile of a conformational transition pathway in Escherichia coli adenylate kinase can be characterized in a high-dimensional space. The minimum free energy paths of the conformational transitions in adenylate kinase were explored by the on-the-fly string method in 20-dimensional space spanned by the 20 largest-amplitude principal modes, and the free energy and various kinds of average physical quantities along the pathways were successfully evaluated by the MBAR method. The influence of ligand binding on the pathways was characterized in terms of rigid-body motions of the lid-shaped ATP-binding domain (LID) and the AMP-binding (AMPbd) domains. It was found that the LID domain was able to partially close without the ligand, while the closure of the AMPbd domain required the ligand binding. The transition state ensemble of the ligand bound form was identified as those structures characterized by highly specific binding of the ligand to the AMPbd domain, and was validated by unrestrained MD simulations. It was also found that complete closure of the LID domain required the dehydration of solvents around the P-loop. These findings suggest that the interplay of the two different types of domain motion is an essential feature in the conformational transition of the enzyme
Electrophysiological correlates of selective attention: A lifespan comparison
<p>Abstract</p> <p>Background</p> <p>To study how event-related brain potentials (ERPs) and underlying cortical mechanisms of selective attention change from childhood to old age, we investigated lifespan age differences in ERPs during an auditory oddball task in four age groups including 24 younger children (9–10 years), 28 older children (11–12 years), 31 younger adults (18–25), and 28 older adults (63–74 years). In the Unattend condition, participants were asked to simply listen to the tones. In the Attend condition, participants were asked to count the deviant stimuli. Five primary ERP components (N1, P2, N2, P3 and N3) were extracted for deviant stimuli under Attend conditions for lifespan comparison. Furthermore, Mismatch Negativity (MMN) and Late Discriminative Negativity (LDN) were computed as difference waves between deviant and standard tones, whereas Early and Late Processing Negativity (EPN and LPN) were calculated as difference waves between tones processed under Attend and Unattend conditions. These four secondary ERP-derived measures were taken as indicators for change detection (MMN and LDN) and selective attention (EPN and LPN), respectively. To examine lifespan age differences, the derived difference-wave components for attended (MMN and LDN) and deviant (EPN and LPN) stimuli were specifically compared across the four age groups.</p> <p>Results</p> <p>Both primary and secondary ERP components showed age-related differences in peak amplitude, peak latency, and topological distribution. The P2 amplitude was higher in adults compared to children, whereas N2 showed the opposite effect. P3 peak amplitude was higher in older children and younger adults than in older adults. The amplitudes of N3, LDN, and LPN were higher in older children compared with both of the adult groups. In addition, both P3 and N3 peak latencies were significantly longer in older than in younger adults. Interestingly, in the young adult sample P3 peak amplitude correlated positively and P3 peak latency correlated negatively with performance in the Identical Picture test, a marker measure of fluid intelligence.</p> <p>Conclusion</p> <p>The present findings suggest that patterns of event-related brain potentials are highly malleable within individuals and undergo profound reorganization from childhood to adulthood and old age.</p
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