3,919 research outputs found

    Direct Measurement of van der Waals and Diffuse Double-Layer Forces between Titanium Dioxide Surfaces Produced by Atomic Layer Deposition

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    The van der Waals forces between titanium dioxide surfaces produced by atomic layer deposition (ALD) at the isoelectric point have been measured and found to agree with the calculated interaction using Lifshitz theory. It is shown that under the right conditions very smooth ALD surfaces are produced. At pH values slightly below and above the isoelectric point, a repulsive diffuse double-layer repulsion was observed and is attributed to positive and negative charging of the surfaces, respectively. At high pH, it was found that the forces remained repulsive up until contact and no van der Waals attraction or adhesion was evident. The absence of an attraction cannot be explained by the presence of hydration forces.© 2012, American Chemical Societ

    Stapled Peptides as HIF‐1α/p300 Inhibitors: Helicity Enhancement in the Bound State Increases Inhibitory Potency

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    Protein–protein interactions (PPIs) control virtually all cellular processes and have thus emerged as potential targets for development of molecular therapeutics. Peptide‐based inhibitors of PPIs are attractive given that they offer recognition potency and selectivity features that are ideal for function, yet, they do not predominantly populate the bioactive conformation, frequently suffer from poor cellular uptake and are easily degraded, for example, by proteases. The constraint of peptides in a bioactive conformation has emerged as a promising strategy to mitigate against these liabilities. In this work, using peptides derived from hypoxia‐inducible factor 1 (HIF‐1α) together with dibromomaleimide stapling, we identify constrained peptide inhibitors of the HIF‐1α/p300 interaction that are more potent than their unconstrained sequences. Contrary to expectation, the increased potency does not correlate with an increased population of an α‐helical conformation in the unbound state as demonstrated by experimental circular dichroism analysis. Rather, the ability of the peptide to adopt a bioactive α‐helical conformation in the p300 bound state is better supported in the constrained variant as demonstrated by molecular dynamics simulations and circular dichroism difference spectra

    Computing value from quality and quantity in human decision making

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    How organisms learn the value of single stimuli through experience is well described. In many decisions, however, value estimates are computed 'on the fly', by combining multiple stimulus attributes. The neural basis of this computation is poorly understood. Here we explore a common scenario in which decision-makers must combine information about quality and quantity to determine the best option. Using fMRI, we examined the neural representation of quality, quantity, and their integration into an integrated subjective value signal in humans of both genders. We found that activity within Inferior Frontal Gyrus (IFG) correlated with offer quality, whilst activity in the Intra Parietal Sulcus (IPS) specifically correlated with offer quantity. Several brain regions, including the Anterior Cingulate Cortex (ACC), were sensitive to an interaction of quality and quantity. However, the ACC was uniquely activated by quality, quantity, and their interaction, suggesting this region provides a substrate for flexible computation of value from both quality and quantity. Furthermore, ACC signals across subjects correlated with the strength of quality and quantity signals in IFG and IPS respectively. ACC tracking of subjective value also correlated with choice predictability. Finally, activity in the ACC was elevated for choice trials, suggesting that ACC provides a nexus for the computation of subjective value in multi-attribute decision making.SIGNIFICANCE STATEMENTWould you prefer 3 apples or 2 oranges? Many choices we make each day require us to weigh up the quality and quantity of different outcomes. Using fMRI, we show that option quality is selectively represented in the Inferior Frontal Gyrus (IFG), whilst option quantity correlates with areas of the Intra Parietal Sulcus (IPS) which have previously been associated with numerical processing. We show that information about the two is integrated into a value signal in the Anterior Cingulate Cortex (ACC), and the fidelity of this integration predicts choice predictability. Our results demonstrate how on-the-fly value estimates are computed from multiple attributes in human value-based decision making

    Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.

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    BACKGROUND\ud \ud Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud \ud METHODS\ud \ud Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud \ud RESULTS\ud \ud The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud \ud CONCLUSIONS\ud \ud The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended

    Gastroesophageal reflux disease in 2006: The imperfect diagnosis

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    There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Clearly, barium contrast fluoroscopy is superior to any other test in defining the anatomy of the upper gastrointestinal (UGI) tract. Although fluoroscopy can demonstrate gastroesophageal reflux (GER), this observation does not equate to GERD. Fluoroscopy time should not be prolonged to attempt to demonstrate GER during barium contrast radiography. There are no data to justify prolonging fluoroscopy time to perform provocative maneuvers to demonstrate reflux during barium contrast UGI series. Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring, and a significant percentage of patients with abnormal esophageal acid exposure have no or minimal clinical symptoms of reflux. Abnormal acid exposure defined by pH monitoring over a 24-h period does not equate to GERD. In clinical practice presumptive diagnosis of GERD is reasonably assumed by substantial reduction or elimination of suspected reflux symptoms during therapeutic trial of acid reduction therapy

    Small zinc doped iron oxide tracers for magnetic particle imaging

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    Magnetic particle imaging (MPI) has garnered significant attention in biomedical imaging research due to its excellent signal intensity that is generated directly from superparamagnetic iron oxide nanoparticles (SPIONs). Small nanoparticle tracers with high saturation magnetisation are crucial for MPI as they can prolong circulation, crossing the blood brain barrier and enhance cellular uptake. In this work, we demonstrate small zinc doped iron oxide nanoparticles (Zn-IONPs) are excellent MPI tracers. Our Zn-IONPs exhibited up to 37 % and 64% enhancement in saturation magnetisation (Msat) value and MPI signal intensity respectively compared to Fe3O4 of the same size. As a result, the polymer encapsulated Zn-IONPs achieved up to 2.7-fold enhancement in MPI signal intensity compared to VivoTrax. Furthermore, these polymer encapsulated NPs were also determined to be non-toxic hence making these Zn-IONPs ideal for many biomedical applications in MPI where small size is critical to prolong circulation time and crossing the blood brain barrier

    Logarithmic correction to BH entropy as Noether charge

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    We consider the role of the type-A trace anomaly in static black hole solutions to semiclassical Einstein equation in four dimensions. Via Wald's Noether charge formalism, we compute the contribution to the entropy coming from the anomaly induced effective action and unveil a logarithmic correction to the Bekenstein-Hawking area law. The corrected entropy is given by a seemingly universal formula involving the coefficient of the type-A trace anomaly, the Euler characteristic of the horizon and the value at the horizon of the solution to the uniformization problem for Q-curvature. Two instances are examined in detail: Schwarzschild and a four-dimensional massless topological black hole. We also find agreement with the logarithmic correction due to one-loop contribution of conformal fields in the Schwarzschild background.Comment: 14 pages, JHEP styl

    QCD axion and quintessential axion

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    The axion solution of the strong CP problem is reviewed together with the other strong CP solutions. We also point out the quintessential axion(quintaxion) whose potential can be extremely flat due to the tiny ratio of the hidden sector quark mass and the intermediate hidden sector scale. The quintaxion candidates are supposed to be the string theory axions, the model independent or the model dependent axions.Comment: 15 pages. Talk presented at Castle Ringberg, June 9-14, 200
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