3,194 research outputs found

    Bound and free waves in non-collinear second harmonic generation

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    We analyze the relationship between the bound and the free waves in the noncollinear SHG scheme, along with the vectorial conservation law for the different components arising when there are two pump beams impinging on the sample with two different incidence angles. The generated power is systematically investigated, by varying the polarization state of both fundamental beams, while absorption is included via the Herman and Hayden correction terms. The theoretical simulations, obtained for samples which are some coherence length thick show that the resulting polarization mapping is an useful tool to put in evidence the interference between bound and free waves, as well as the effect of absorption on the interference patternComment: 10 pages, 7 figure. to be published on Optics Expres

    MEMS/ECD Method for Making Bi(2-x)Sb(x)Te3 Thermoelectric Devices

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    A method of fabricating Bi(2-x)Sb(x)Te3-based thermoelectric microdevices involves a combination of (1) techniques used previously in the fabrication of integrated circuits and of microelectromechanical systems (MEMS) and (2) a relatively inexpensive MEMS-oriented electrochemical-deposition (ECD) technique. The present method overcomes the limitations of prior MEMS fabrication techniques and makes it possible to satisfy requirements

    Novel fused arylpyrimidinone based allosteric modulators of the M1 muscarinic acetylcholine receptor

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    Benzoquinazolinone 1 is a positive allosteric modulator (PAM) of the M1 muscarinic acetylcholine receptor (mAChR), which is significantly more potent than the prototypical PAM, 1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline- 3-carboxylic acid (BQCA). In this study, we explored the structural determinants that underlie the activity of 1 as a PAM of the M1 mAChR. We paid particular attention to the importance of the tricyclic scaffold of compound 1, for the activity of the molecule. Complete deletion of the peripheral fused benzene ring caused a significant decrease in affinity and binding cooperativity with acetylcholine (ACh). This loss of affinity was rescued with the addition of either one or two methyl groups in the 7- and/or 8-position of the quinazolin-4(3H)-one core. These results demonstrate that the tricyclic benzo[h]quinazolin-4(3H)-one core could be replaced with a quinazolin-4(3H)-one core and maintain functional affinity. As such, the quinazolin-4(3H)-one core represents a novel scaffold to further explore M1 mAChR PAMs with improved physicochemical properties

    An in vitro model of murine middle ear epithelium.

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    Otitis media (OM) or middle ear inflammation is the most common pediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well characterised in vitro model of the middle ear (ME) epithelium that replicates the complex cellular composition of the middle ear. Here we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs) at air liquid interface (ALI) that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We could show that the mMECs supported the growth of the otopathogen, NTHi, suggesting that the model can be succesfully utilised to study host pathogen interactions in the middle ear. Overall, our mMEC culture system can help better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling underpinning OM development

    4-Phenylpyridin-2-one derivatives: a novel class of positive allosteric modulator of the M1 muscarinic acetylcholine receptor

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    Positive allosteric modulators (PAMs) of the M1 muscarinic acetylcholine receptor (M1 mAChR) are a promising strategy for the treatment of the cognitive deficits associated with diseases including Alzheimer’s and schizophrenia. Herein, we report the design, synthesis, and characterization of a novel family of M1 mAChR PAMs. The most active compounds of the 4-phenylpyridin-2-one series exhibited comparable binding affinity to the reference compound, 1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (BQCA) (1), but markedly improved positive cooperativity with acetylcholine, and retained exquisite selectivity for the M1 mAChR. Furthermore, our pharmacological characterization revealed ligands with a diverse range of activities, including modulators that displayed both high intrinsic efficacy and PAM activity, those that showed no detectable agonism but robust PAM activity and ligands that displayed robust allosteric agonism but little modulatory activity. Thus, the 4-phenylpyridin-2-one scaffold offers an attractive starting point for further lead optimization

    NIR Femtosecond Control of Resonance-Mediated Generation of Coherent Broadband UV Emission

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    We use shaped near-infrared (NIR) pulses to control the generation of coherent broadband ultraviolet (UV) radiation in an atomic resonance-mediated (2+1) three-photon excitation. Experimental and theoretical results are presented for phase controlling the total emitted UV yield in atomic sodium (Na). Based on our confirmed understanding, we present a new simple scheme for producing shaped femtosecond pulses in the UV/VUV spectral range using the control over atomic resonance-mediated generation of third (or higher order) harmonic.Comment: 14 pages, 4 figure

    Optimising locational access of deprived populations to farmers’ markets at a national scale: one route to improved fruit and vegetable consumption?

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    Background. Evidence suggests that improved locational access to farmers’ markets increases fruit and vegetable (FV) consumption, particularly for low-income groups. Therefore, we modelled potential alternative distributions of farmers’ markets in one country (New Zealand) to explore the potential impact for deprived populations and an indigenous population (Māori).Methods. Data were collected on current farmers’ markets (n = 48), population distributions, area deprivation, and roads. Geographic analyses were performed to optimize market locations for the most deprived populations.Results. We found that, currently, farmers’ markets provided fairly poor access for the total population: 7% within 12.5 km (15 min driving time); 5% within 5 km; and 3% within 2 km. Modelling the optimal distribution of the 48 markets substantially improved access for the most deprived groups: 9% (vs 2% currently) within 12.5 km; 5% (vs 1%) within 5 km; and 3% (vs 1%) within 2 km. Access for Māori also improved: 22% (vs 7%) within 12.5 km; 12% (vs 4%) within 5 km; and 6% (vs 2%) within 2 km. Smaller pro-equity results arose from optimising the locations of the 18 least pro-equity markets or adding 10 new markets.Conclusion. These results highlight the potential for improving farmers’ market locations to increase accessibility for groups with low FV consumption. Given that such markets are easily established and relocated, local governments could consider these results to inform decisions, including subsidies for using government land and facilities. Such results can also inform central governments planning around voucher schemes for such markets and exempting them from taxes (e.g., VAT/GST)

    The effectiveness of neuromuscular warm-up strategies, that require no additional equipment, for preventing lower limb injuries during sports participation: a systematic review

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    PMCID: PMC3408383The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/75. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

    Investigation of the growth parameters of hydrothermal ZnO nanowires for scale up applications

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    Zinc oxide nano-wires (ZnO NWs) are synthesized reproducibly with high yield via a low temperature hydrothermal technique. The influence of the growth duration time, growth temperature, zinc precursor and base concentration of Na2CO3 on the morphology of NWs is investigated. The growth products are characterised using scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL). SEM analysis shows that the optimum growth temperature is 140 °C and finds that length and diameter of ZnO NWs have a relationship with growth duration time and base concentrations of Na2CO3. In addition, it is reported that a high (∼ 90%) yield of ZnO NWs can be synthesised via using any of three different precursors: zinc chloride, zinc acetate and zinc nitrate. TEM and XRD results indicate the high purity and the single crystalline nature of the ZnO NWs. XPS confirms the absence of sodium contaminants on the surface and indicates a near flat band surface condition. PL shows a large visible band in the yellow part of the spectrum, and a small exciton emission peak, indicating a large defect concentration, which is reduced after annealing in air

    Communications Biophysics

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    Contains research objectives and summary of research on nine research projects split into four sections.National Institutes of Health (Grant 5 ROI NS11000-03)National Institutes of Health (Grant 1 P01 NS13126-01)National Institutes of Health (Grant 1 RO1 NS11153-01)National Institutes of Health (Grant 2 R01 NS10916-02)Harvard-M.I.T. Rehabilitation Engineering CenterU. S. Department of Health, Education, and Welfare (Grant 23-P-55854)National Institutes of Health (Grant 1 ROl NS11680-01)National Institutes of Health (Grant 5 ROI NS11080-03)M.I.T. Health Sciences Fund (Grant 76-07)National Institutes of Health (Grant 5 T32 GM07301-02)National Institutes of Health (Grant 5 TO1 GM01555-10
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