AaeAP1 and AaeAP2: Novel Antimicrobial Peptides from the Venom of the Scorpion, Androctonus aeneas: Structural Characterisation, Molecular Cloning of Biosynthetic Precursor-Encoding cDNAs and Engineering of Analogues with Enhanced Antimicrobial and Anticancer Activities

The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3'- and 5'-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation.

Gold nanoparticle surface functionalization: a necessary requirement in the development of novel nanotherapeutics

With several gold nanoparticle-based therapies currently undergoing clinical trials, these treatments may soon be in the clinic as novel anticancer agents. Gold nanoparticles are the subject of a wide ranging international research effort with preclinical studies underway for multiple applications including photoablation, diagnostic imaging, radiosensitization and multifunctional drug-delivery vehicles. These applications require an increasingly complex level of surface modification in order to achieve efficacy and limit off-target toxicity. This review will discuss the main obstacles in relation to surface functionalization and the chemical approaches commonly utilized. Finally, we review a range of recent preclinical studies that aim to advance gold nanoparticle treatments toward the clinic.

Processes influencing the destruction of microcystin-LR by TiO2 photocatalysis

We have previously reported the effectiveness of TiO₂ photocatalysis in the destruction of the cyanotoxin microcystin-LR [P.K.J. Robertson, L.A. Lawton, B. Münch, J. Rouzade, J. Chem. Soc., Chem. Commun., 4 (1997) 393; P.K.J. Robertson, L.A. Lawton, B. Münch, B.J.P.A. Cornish, J. Adv. Oxid. Technol., in press]. In this paper we report an investigation of factors which influence the rate of the toxin destruction at the catalyst surface. A primary kinetic isotope effect of approximately 3 was observed when the destruction was performed in a heavy water solvent. Hydroxylated compounds were observed as products of the destruction process. No destruction was observed when the process was investigated under a nitrogen atmosphere.

Vlasov-kinetic computer simulations of electrostatic waves in dusty plasmas: an overview of recent results

A series of numerical simulations based on a recurrence-free Vlasov kinetic model using kinetic phase point trajectories are presented. Electron-ion plasmas and three-component (electron-ion-dust) dusty or complex plasmas are considered, via independent simulations. Considering all plasma components modeled through a kinetic approach, the linear and nonlinear behavior of ion-acoustic excitations is investigated. Maxwellian and kappa-type (superthermal) distribution functions are assumed, as initial conditions, in separate simulations for the sake of comparison. The focus is on the parametric dependence of ion-acoustic waves on the electron-to-ion temperature ratio and on the dust concentration. © 2014 EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg.

Revision over Partial Pre-orders: A Postulational Study

Belief revision is the process that incorporates, in a consistent way,
a new piece of information, called input, into a belief base. When both belief
bases and inputs are propositional formulas, a set of natural and rational properties, known as AGM postulates, have been proposed to define genuine revision operations. This paper addresses the following important issue : How to revise a partially pre-ordered information (representing initial beliefs) with a new partially pre-ordered information (representing inputs) while preserving AGM postulates? We first provide a particular representation of partial pre-orders (called units) using the concept of closed sets of units. Then we restate AGM postulates in this framework by defining counterparts of the notions of logical entailment and logical consistency. In the second part of the paper, we provide some examples of revision operations that respect our set of postulates. We also prove that our revision methods extend well-known lexicographic revision and natural revision for both cases where the input is either a single propositional formula or a total pre-order.

(Re) making trajectories: Eviction, control and power

The City of Cairo's experienced a major shift in its urban planning attitude and practice since the mid 1970s which mostly validated elements of economic planning while neutralizing its social aspects. This ad hoc approach escalated conflict in planning politics over the control of space between tiers of the planning institution and the locals leading to rigorous planning actions among major stakeholders such as eviction and control of spaces. The article examines how institutional claims over space reassembled alternative definitions of quality of life in one of Cairo's oldest quarters, and how ambitious planning schemes were mostly driven by entrepreneurial rather than societal. Based on first-hand interviews and visuals, the article aims to reveal the local's struggle to survive such interventions with attention to their daily negotiations in place.

Functional genomics to identify therapeutic prophylactic targets

Infectious diseases are a leading cause of global human mortality. The use of antimicrobials remains the most common strategy for treatment. However, the isolation of pathogens resistant to virtually all antimicrobials makes it urgent to develop effective therapeutics based on new targets. Here we review a new drug discovery paradigm focusing on identifying and targeting host factors important for infection as well as pathogen determinants involved in disease progression. We summarize innovative strategies which by combining bioinformatics with transcriptomics and chemical genetics have already identified host factors essential for pathogen entry, survival and replication. We describe how the discovery of RNA interference which allows loss-of-function studies has facilitated functional genomic studies in human cells. It is expected that these studies will identify targets to be used as host-directed drug therapy which, together with antimicrobials targeting microbial virulence factors, will efficiently eliminate the invading pathogen.

Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients

Background: The identification of pre-clinical microvascular damage in hypertension by non-invasive techniques has proved frustrating for clinicians. This proof of concept study investigated whether entropy, a novel summary measure for characterizing blood velocity waveforms, is altered in participants with hypertension and may therefore be useful in risk stratification.

Methods: Doppler ultrasound waveforms were obtained from the carotid and retrobulbar circulation in 42 participants with uncomplicated grade 1 hypertension (mean systolic/diastolic blood pressure (BP) 142/92 mmHg), and 26 healthy controls (mean systolic/diastolic BP 116/69 mmHg). Mean wavelet entropy was derived from flow-velocity data and compared with traditional haemodynamic measures of microvascular function, namely the resistive and pulsatility indices.

Results: Entropy, was significantly higher in control participants in the central retinal artery (CRA) (differential mean 0.11 (standard error 0.05 cms(-1)), CI 0.009 to 0.219, p 0.017) and ophthalmic artery (0.12 (0.05), CI 0.004 to 0.215, p 0.04). In comparison, the resistive index (0.12 (0.05), CI 0.005 to 0.226, p 0.029) and pulsatility index (0.96 (0.38), CI 0.19 to 1.72, p 0.015) showed significant differences between groups in the CRA alone. Regression analysis indicated that entropy was significantly influenced by age and systolic blood pressure (r values 0.4-0.6). None of the measures were significantly altered in the larger conduit vessel.

Conclusion: This is the first application of entropy to human blood velocity waveform analysis and shows that this new technique has the ability to discriminate health from early hypertensive disease, thereby promoting the early identification of cardiovascular disease in a young hypertensive population.

The Intersection of Religious Autonomy and Religious Symbols: Setting the Stage

Two sets of issues in the area of law and religion have generated a large share of attention and controversy across a wide number of countries and jurisdictions in recent years. The first set of issues relates to the autonomy of churches and other religiously affiliated entities such as schools and social service organisations in their hiring and personnel decisions, involving the question of how far, if at all, such entities should be free from the influence and oversight of the state. The second set of issues involves the presence of religious symbols in the public sphere, such as in state schools or on public lands, involving the question of how far the state should be free from the influence of religion. Although these issues – freedom of religion from the state, and freedom of the state from religion – could be viewed as opposite sides of the same coin, they are almost always treated as separate lines of inquiry, and the implications of each for the other have not been the subject of much scrutiny. In this Introduction, we consider whether insights might be drawn from thinking about these issues both from a comparative law perspective and also from considering these two lines of cases together.

Further evidence for a bifactor solution for the Consideration of Future Consequences Scale: Measurement and conceptual implications

The Consideration of Future Consequences construct has been found to relate meaningfully to several positive outcomes in temporal research. Researchers have proposed 1-factor, 2-factor, and bifactor solutions to the Consideration of Future Consequences Scale (CFCS). Using 313 British University undergraduates, we tested four competing models: (a) a 12-item unidimensional model, (b) a model fitted for two uncorrelated factors (CFC-Immediate and CFC-Future), (c) a model fitted for two correlated factors (CFC-I and CFC-F), and (d) a bifactor model. Results supported the bifactor model, suggesting that the two hypothesized factors are better understood as grouping factors. Accordingly, the present study supports the CFCS as a unidimensional global future orientation measure. These results have important implications for the study of future orientation using the CFCS. Researchers using the CFCS are encouraged to examine a bifactor solution for the scores.

Application-Level Energy Awareness for OpenMP

Power, and consequently energy, has recently attained first-class system resource status, on par with conventional metrics such as CPU time. To reduce energy consumption, many hardware- and OS-level solutions have been investigated. However, application-level information - which can provide the system with valuable insights unattainable otherwise - was only considered in a handful of cases. We introduce OpenMPE, an extension to OpenMP designed for power management. OpenMP is the de-facto standard for programming parallel shared memory systems, but does not yet provide any support for power control. Our extension exposes (i) per-region multi-objective optimization hints and (ii) application-level adaptation parameters, in order to create energy-saving opportunities for the whole system stack. We have implemented OpenMPE support in a compiler and runtime system, and empirically evaluated its performance on two architectures, mobile and desktop. Our results demonstrate the effectiveness of OpenMPE with geometric mean energy savings across 9 use cases of 15 % while maintaining full quality of service.

Is differential phytochelatin production related to decreased arsenate influx in arsenate tolerant Holcus lanatus?

Phytochelatins (PCs) are required for arsenic (As) detoxification in nontolerant plants. In addition, a role for PCs in arsenate tolerance has recently been proven, with tolerant plants able to accumulate significantly higher concentrations of As-PC complexes at equivalent levels of stress than nontolerant plants. The relationship between arsenate influx and PC production in tolerant and non-tolerant Holcus lanatus plants was determined in this study, along with an investigation of the effect of inhibition of PC synthesis by buthionine sulfoximine (BSO) on arsenate tolerance. A strong correlation between PC production and arsenate influx was demonstrated in arsenate-tolerant plants. In addition, inhibition of PC synthesis by BSO in tolerant plants increased arsenate sensitivity to that of the nontolerant clone. This dramatic reduction in tolerance proves that PC production is an essential component of the arsenate tolerance mechanism in H. lanatus. This study proposes that while there is a single major gene for arsenate tolerance, hypostatic modifiers are also in operation, affecting the expression of the tolerance character. © New Phytologist (2002).

The frequency of Environmental Quality Standard (EQS) exceedance for chlorinated organic pollutants in rivers of the Humber catchments

The southern industrial rivers (Aire, Calder, Don and Trent) feeding the Humber estuary were routinely monitored for a range of chlorinated micro- organic contaminants at least once a week over a 1.5-year period. Environmental Quality Standards (EQSs) for inland waters were set under the European Economic Community for a limited number of problematic contaminants (18). The results of the monitoring program for seven classes of chlorinated pollutants on the EQS list are presented in this study. All compounds were detected frequently with the exception of hexachlorobutadiene (where only one detectable measurement out of 280 individual samples occurred). In general, the rivers fell into two classes with respect to their contamination patterns. The Aire and Calder carried higher concentrations of micro- pollutants than the Don and Trent, with the exception of hexachlorobenzene (HCB). For Σ hexachlorocyclohexane (HCH) isomers (α + γ) and for dieldrin, a number of samples (~ 5%) exceeded their EQS for both the Aire and Calder. Often, ΣHCH concentrations were just below the EQS level. Levels of p,p'- DDT on occasions approached the EQS for these two rivers, but only one sample (out of 140) exceeded the EQS. No compounds exceeded their EQS levels on the Don and Trent. Analysis of the ratio of γ HCH/αHCH indicated that the source of HCH for the Don and Trent catchments was primarily lindane (γHCH) and, to a lesser extent, technical HCH (mixture of HCH isomers, dominated by α HCH), while the source(s) for the Aire and Calder had a much higher contribution from technical HCH.

Polymorphism and physiology of arsenate tolerance in Holcus lanatus L. from an uncontaminated site

The polymorphism of arsenate tolerance in a Holcus lanatus L. population from an uncontaminated soil was investigated and a high percentage of tolerant individuals (65%) was found in the population studied. Influx of arsenate was highly correlated to arsenate tolerance within the population, with the most tolerant individuals having the lowest rates of arsenate influx. Isotherms for the high affinity arsenate uptake systems were determined in six tolerant and six non-tolerant genotypes. Tolerant plants had the lowest rates of arsenate influx. This was achieved by adaptation of the V_max of arsenate influx with the V_max of the high affinity uptake system saturating at lower substrate concentrations in the tolerant plants. The polymorphism is discussed with relation to adaptation to the extreme environments to which the plants are subjected on mine-spoil soils. © 1992 Kluwer Academic Publishers.