Microfiltration of water-based paint effluents

This paper deals with recovery of water from the effluent in a paint factory in Kuala Lumpur for reuse using microfiltration technique.

Thermotropic phase boundaries in classic ferroelectrics

High-performance piezoelectrics are lead-based solid solutions that exhibit a so-called morphotropic phase boundary, which separates two competing phases as a function of chemical composition; as a consequence, an intermediate low-symmetry phase with a strong piezoelectric effect arises. In search for environmentally sustainable lead-free alternatives that exhibit analogous characteristics, we use a network of competing domains to create similar conditions across thermal inter-ferroelectric transitions in simple, lead-free ferroelectrics such as BaTiO 3 and KNbO 3. Here we report the experimental observation of thermotropic phase boundaries in these classic ferroelectrics, through direct imaging of low-symmetry intermediate phases that exhibit large enhancements in the existing nonlinear optical and piezoelectric property coefficients. Furthermore, the symmetry lowering in these phases allows for new property coefficients that exceed all the existing coefficients in both parent phases. Discovering the thermotropic nature of thermal phase transitions in simple ferroelectrics thus presents unique opportunities for the design of 'green' high-performance materials.

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 1: Development of a potent and CNS penetrant [3.1.0]-based lead

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach that provided a robust intellectual property position, in lieu of a traditional, expensive HTS campaign. Members within this new [3.1.0]​-​based series displayed excellent GlyT1 potency, selectivity, free fraction, CNS penetration and efficacy in a preclin. model of schizophrenia (prepulse inhibition)​.

How simple grazing rules can lead to persistent boundaries in vegetation communities.

Natural landscape boundaries between vegetation communities are dynamically influenced by the selective grazing of herbivores. Here we show how this may be an emergent property of very simple animal decisions, without the need for any sophisticated choice rules etc., using a model based on biased diffusion. Animal grazing intensity is coupled with plant competition, resulting in reaction-diffusion dynamics, from which stable boundaries spontaneously emerge. In the model, animals affect their resources by both consumption and trampling. It is assumed that forage consists of two heterogeneously distributed competing resource species, one that is preferred (grass) over the other (heather) by the animals. The solutions to the resulting system of differential equations for three cases a) optimal foraging, b) random walk foraging and c) taxis-diffusion are presented. Optimal and random foraging gave unrealistic results, but taxis-diffusion accorded well with field observations. Persistent boundaries between patches of near-monoculture vegetation were predicted, with these boundaries drifting in response to overall grazing pressure (grass advancing with increased grazing and vice versa). The reaction-taxis-diffusion model provides the first mathematical explanation for such vegetation mosaic dynamics and the parameters of the model are open to experimental testing.

Accommodative dysfunction in children with cerebral palsy: a population based study

Purpose. To determine the prevalence, nature, and degree of accommodative dysfunction among children with different types and severities of cerebral palsy (CP) in Northern Ireland. Methods. Ninety subjects with CP (aged 4–15 years) were recruited through the Northern Ireland CP Register (NICPR). Modified Nott dynamic retinoscopy was used to measure lag and lead of accommodation at three test distances: 25 cm (4 D), 16.7 cm (6 D), and 10 cm (10 D) with the distance correction in place. Accommodative function was also assessed in an age-matched control group (n = 125) for comparison. Each subject’s neurologic status was derived from the NICPR. Results. Children with CP demonstrate significantly reduced accommodative responses compared with their neurologically normal peers. Of the subjects with CP, 57.6% demonstrated an accommodative lag outside normal limits at one or more distances. Reduced accommodative responses were significantly associated with more severe motor and intellectual impairments (ANOVA P = 0.001, P < 0.01, respectively). Conclusions. Brain injury such as that present in CP has a significant impact on accommodative function. These findings have implications for the optometric care of children with CP and inform our understanding of the impact of early brain injury on visual development.

Effect of ternary phosphate-based glass compositions on osteoblast and osteoblast-like prolferation, differentiation and death in vitro

There is currently a need to expand the range of graft materials available to orthopaedic surgeons. This study investigated the effect of ternary phosphate based glass (PBG) compositions on the behaviour of osteoblast and osteoblast-like cells. PBGs of the formula in mol% P2O5 (50)-CaO (50-X)-Na2O (X), where X was either 2, 4, 6, 8 or 10 were produced and their influence on the proliferation, differentiation and death in vitro of adult human bone marrow stromal cells (hBMSCs) and human fetal osteoblast 1.19 (HFOB 1.19) cells were assessed. Tissue culture plastic (TCP) and hydroxyapatite (HA) were used as controls. Exposure to PBGs in culture inhibited cell adhesion, proliferation and increased cell death in both cell types studied. There was no significant difference in %cell death between the PBGs which was significantly greater than the controls. However, compared to other PBGs, a greater number of cells was found on the 48 mol% CaO which may have been due to either increased adherence, proliferation or both. This composition was capable of supporting osteogenic proliferation and early differentiation and supports the notion that chemical modification of the glass could to lead to a more biologically compatible substrate with the potential to support osteogenic grafting. Realisation of this potential should lead to the development of novel grafting strategies for the treatment of problematic bone defects.

A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods.

The coronavirus main protease, Mpro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential Mpro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed Mpro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a Ki value of 35.3 M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.

Balanced class e amplifier based multimode modulator

In this paper we present an adaptation to the classical I/Q modulator topology which simultaneously allows it to operate both as a multi-modulation standard modulator, and as a high efficiency balanced amplifier. This is made possible by concurrently exploiting the ability of the Class E amplifiers to produce variable output power at maximum power added efficiency, PAE, by simple dc bias control while faithfully reproducing phase encoded signals. Experimental evidence for the behaviour of the modulator when operated in QPSK mode at 2.33 GHz with a 1 Msymbol/s rate shows that Error Vector Magnitude of less than 5% with amplifier PAE of 65% is possible. The multimode modulator presented here should lead to significantly reduced complexity, enhanced functionality transceivers for use in dc power sensitive handheld wireless applications. © 2007 EuMA.

Ligand and structure-based methodologies for the prediction of the activity of G protein-coupled receptor ligands

Accurate in silico models for the quantitative prediction of the activity of G protein-coupled receptor (GPCR) ligands would greatly facilitate the process of drug discovery and development. Several methodologies have been developed based on the properties of the ligands, the direct study of the receptor-ligand interactions, or a combination of both approaches. Ligand-based three-dimensional quantitative structure-activity relationships (3D-QSAR) techniques, not requiring knowledge of the receptor structure, have been historically the first to be applied to the prediction of the activity of GPCR ligands. They are generally endowed with robustness and good ranking ability; however they are highly dependent on training sets. Structure-based techniques generally do not provide the level of accuracy necessary to yield meaningful rankings when applied to GPCR homology models. However, they are essentially independent from training sets and have a sufficient level of accuracy to allow an effective discrimination between binders and nonbinders, thus qualifying as viable lead discovery tools. The combination of ligand and structure-based methodologies in the form of receptor-based 3D-QSAR and ligand and structure-based consensus models results in robust and accurate quantitative predictions. The contribution of the structure-based component to these combined approaches is expected to become more substantial and effective in the future, as more sophisticated scoring functions are developed and more detailed structural information on GPCRs is gathered.

Rational Design of Acridine-Based Ligands with Selectivity for Human Telomeric Quadruplexes

Structure-based modeling methods have been used to design a series of disubstituted triazole-linked acridine compounds with selectivity for human telomeric quadruplex DNAs. A focused library of these compounds was prepared using click chemistry and the selectivity concept was validated against two promoter quadruplexes from the c-kit gene with known molecular structures, as well as with duplex DNA using a FRET-based melting method. Lead compounds were found to have reduced effects on the thermal stability of the c-kit quadruplexes and duplex DNA structures. These effects were further explored with a series of competition experiments, which confirmed that binding to duplex DNA is very low even at high duplex:telomeric quadruplex ratios. Selectivity to the c-kit quadruplexes is more complex, with some evidence of their stabilization at increasing excess over human telomeric quadruplex DNA. Selectivity is a result of the dimensions of the triazole-acridine compounds; and in particular the separation of the two alkyl-amino terminal groups. Both lead compounds also have selective inhibitory effects on the proliferation of cancer cell lines compared to a normal cell line, and one has been shown to inhibit the activity of the telomerase enzyme, which is selectively expressed in tumor cells, where it plays a role in maintaining telomere integrity and cellular immortalization.

Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold

This Letter describes the hit-to-lead progression and SAR of a series of biphenyl acetylene compounds derived from an HTS screening campaign targeting the mGlu(5) receptor. 'Molecular switches' were identified that modulated modes of pharmacology, and several compounds within this series were shown to be efficacious in reversal of amphetamine induced hyperlocomotion in rats after ip dosing, a preclinical model that shows similar positive effects with known antipsychotic agents. Published by Elsevier Ltd.

Ecohydrological feedbacks confound peat-based climate reconstructions

Water-table reconstructions from Holocene peatlands are increasingly being used as indicators of terrestrial palaeoclimate in many regions of the world. However, the links between peatland water tables, climate, and long-term peatland development are poorly understood. Here we use a combination of high-resolution proxy climate data and a model of long-term peatland development to examine the relationship between rapid hydrological fluctuations in peatlands and climatic forcing. We show that changes in water-table depth can occur independently of climate forcing. Ecohydrological feedbacks inherent in peatland development can lead to a degree of homeostasis that partially disconnects peatland water-table behaviour from external climatic influences. We conclude by suggesting that further work needs to be done before peat-based climate reconstructions can be used to test climate models.

Web-based social movements contesting marketing strategy: Mobilization of multiple actors and rhetorical strategies

Previous studies suggest that marketing strategy is developed and used to mobilise and configure the actions of firm actors, creating a set of stabilising activities focused on the firm–customer dyad. Destabilising forces precipitated by the Internet and associated digital technologies involving contention and disruption by multiple actors are much less prevalent in the marketing literature. The central point we advance is that rather than marketing strategy being a controlled and stabilising force for firms in their relationships with customers, it can often lead to socially produced spaces where consumers and, importantly, other multiple actors form a social movement to actively attempt to destabilise it and contest its legitimacy. Using an innovative research approach, the findings of this study show how social movements proactively enrol and mobilise a wide range of relevant actors into a network of influence. Critical to this are rhetorical strategies, acting as important levers in attempts to destabilise and delegitimise a dominant firm's marketing strategy.

Assessing reproducibility of data obtained with instruments based on continuous measurements

Data obtained with any research tool must be reproducible, a concept referred to as reliability. Three techniques are often used to evaluate reliability of tools using continuous data in aging research: intraclass correlation coefficients (ICC), Pearson correlations, and paired t tests. These are often construed as equivalent when applied to reliability. This is not correct, and may lead researchers to select instruments based on statistics that may not reflect actual reliability. The purpose of this paper is to compare the reliability estimates produced by these three techniques and determine the preferable technique. A hypothetical dataset was produced to evaluate the reliability estimates obtained with ICC, Pearson correlations, and paired t tests in three different situations. For each situation two sets of 20 observations were created to simulate an intrarater or inter-rater paradigm, based on 20 participants with two observations per participant. Situations were designed to demonstrate good agreement, systematic bias, or substantial random measurement error. In the situation demonstrating good agreement, all three techniques supported the conclusion that the data were reliable. In the situation demonstrating systematic bias, the ICC and t test suggested the data were not reliable, whereas the Pearson correlation suggested high reliability despite the systematic discrepancy. In the situation representing substantial random measurement error where low reliability was expected, the ICC and Pearson coefficient accurately illustrated this. The t test suggested the data were reliable. The ICC is the preferred technique to measure reliability. Although there are some limitations associated with the use of this technique, they can be overcome.