Bound and free waves in non-collinear second harmonic generation

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

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

Stabilization of peat soil by using envirotac

Peat soil is wet and soft. It is also known as a very soft and difficult soil with high water and organic content, low shear strength, low bearing capacity and their mechanical chemical and biological properties degenerate with time. The characteristics and geotechnical properties of peat soil are mainly related to its high moisture content and high organic content respectively. This is very challenging to geotechnical engineers and construction industry as peat soil characteristic can cause excessive settlement.Soil stabilisation is the process of improving the engineering properties of the soil which will then in return make it more stable. As a result of soil stabilization, the bearing capacity and the strength of the soil will increase with an added bonus of water tightness, resistance to wash out and other properties which will also be improved. In this research, Envirotac polymer is used as the soil stabilizer which is in a form of liquid. This study is done in order to investigate the optimum mix proportion of Envirotac as a liquid stabilizer on Peat soil. The objective of this study was to determine the strength effects of 15%, 30% and 45% of Envirotec on peat sample and to investigate the shrinkage effect of stabilizing peat soil by using Envirotac. A mould sample with a diameter of 50mm and a height of 100mm was prepared. Samples were then tested after 7, 14 and 21 days. The physical properties tests conducted for this research are the Atteberg limits and moisture content test, while the mechanical test was Unconfined Compressive strength (UCS) test. The tests were carried out according to BS 1377: 1990. From the result, 30% Envirotac on peat sample has higher strength from control sample and more economical compare to use 45% Envirotac which had greater shrinkage effec

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

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

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

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

Systematic Assessment of Chemokine Signaling at Chemokine Receptors CCR4, CCR7 and CCR10

Chemokines interact with chemokine receptors in a promiscuous network, such that each receptor can be activated by multiple chemokines. Moreover, different chemokines have been reported to preferentially activate different signalling pathways via the same receptor, a phenomenon known as biased agonism. The human CC chemokine receptors (CCRs) CCR4, CCR7 and CCR10 play important roles in T cell trafficking and have been reported to display biased agonism. To systematically characterize these effects, we analysed G protein- and β-arrestin-mediated signal transduction resulting from stimulation of these receptors by each of their cognate chemokine ligands within the same cellular background. Although the chemokines did not elicit ligand-biased agonism, the three receptors exhibited different arrays of signaling outcomes. Stimulation of CCR4 by either CC chemokine ligand 17 (CCL17) or CCL22 induced β-arrestin recruitment but not G protein-mediated signaling, suggesting that CCR4 has the potential to act as a scavenger receptor. At CCR7, both CCL19 and CCL21 stimulated G protein signaling and β-arrestin recruitment, with CCL19 consistently displaying higher potency. At CCR10, CCL27 and CCL28(4-108) stimulated both G protein signaling and β-arrestin recruitment, whereas CCL28(1-108) was inactive, suggesting that CCL28(4-108) is the biologically relevant form of this chemokine. These comparisons emphasize the intrinsic abilities of different receptors to couple with different downstream signaling pathways. Comparison of these results with previous studies indicates that differential agonism at these receptors may be highly dependent on the cellular context

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

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

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

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)

Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism

By analyzing and simulating inactive conformations of the highly-homologous dopamine D2 and D3 receptors (D2R and D3R), we find that eticlopride binds D2R in a pose very similar to that in the D3R/eticlopride structure but incompatible with the D2R/risperidone structure. In addition, risperidone occupies a sub-pocket near the Na+ binding site, whereas eticlopride does not. Based on these findings and our experimental results, we propose that the divergent receptor conformations stabilized by Na+-sensitive eticlopride and Na+-insensitive risperidone correspond to different degrees of inverse agonism. Moreover, our simulations reveal that the extracellular loops are highly dynamic, with spontaneous transitions of extracellular loop 2 from the helical conformation in the D2R/risperidone structure to an extended conformation similar to that in the D3R/eticlopride structure. Our results reveal previously unappreciated diversity and dynamics in the inactive conformations of D2R. These findings are critical for rational drug discovery, as limiting a virtual screen to a single conformation will miss relevant ligands

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

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