Bystander Signalling: Exploring Clinical Relevance Through New Approaches and New Models

Classical radiation biology research has centred on nuclear DNA as the main target of radiation-induced damage. Over the past two decades, this has been challenged by a significant amount of scientific evidence clearly showing radiation-induced cell signalling effects to have important roles in mediating overall radiobiological response. These effects, generally termed radiation-induced bystander effects (RIBEs) have challenged the traditional DNA targeted theory in radiation biology and highlighted an important role for cells not directly traversed by radiation. The multiplicity of experimental systems and exposure conditions in which RIBEs have been observed has hindered precise definitions of these effects. However, RIBEs have recently been classified for different relevant human radiation exposure scenarios in an attempt to clarify their role in vivo. Despite significant research efforts in this area, there is little direct evidence for their role in clinically relevant exposure scenarios. In this review, we explore the clinical relevance of RIBEs from classical experimental approaches through to novel models that have been used to further determine their potential implications in the clinic. 

Two-Ray Modeling of Recombination Effects in the Presence of a Phase Conjugation Array

This article describes by means of a simple model how signal recombination effects behave under the influence of phase conjugating retrodirective array (RDA) technology. A two-ray ground reflection model is used to predict the operational advantages of RDA technology in multipath rich environments. The simulation results show that advantageous signal recombination occurs due to automatic self-phasing. As the number of elements in the RDA increases, the fading effect normally observed due to out of phase multipath signal is mitigated to the extent that the system approaches that of one operating in a free space environment. © 2013 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:1987–1989, 2013

Identifying optimal feeding habitat and proposed Marine Protected Areas (pMPAs) for the black-legged kittiwake (Rissa tridactyla) suggests a need for complementary management approaches

Marine Protected Areas (MPAs) are an important conservation tool. For marine predators, recent research has focused on the use of Species Distribution Models (SDMs) to identify proposed sites. We used a maximum entropy modelling approach based on static and dynamic oceanographic parameters to determine optimal feeding habitat for black-legged kittiwakes (Rissa tridactyla) at two colonies during two consecutive breeding seasons (2009 and 2010). A combination of Geographic Positioning System (GPS) loggers and Time-Depth Recorders (TDRs) attributed feeding activity to specific locations. Feeding areas were <30 km from the colony, <40 km from land, in productive waters, 25–175m deep. The predicted extent of optimal habitat declined at both colonies between 2009 and 2010 coincident with declines in reproductive success. Whilst the area of predicted optimal habitat changed, its location was spatially stable between years. There was a close match between observed feeding locations and habitat predicted as optimal at one colony (Lambay Island, Republic of Ireland), but a notable mismatch at the other (Rathlin Island, Northern Ireland). Designation of an MPA at Rathlin may, therefore, be less effective than a similar designation at Lambay perhaps due to the inherent variability in currents and sea state in the North Channel compared to the comparatively stable conditions in the central Irish Sea. Current strategies for designating MPAs do not accommodate likely future redistribution of resources due to climate change. We advocate the development of new approaches including dynamic MPAs that track changes in optimal habitat and non-colony specific ecosystem management.

Anisotropy parameters in two-color two-photon above-threshold ionization

We employ the time-dependent R-matrix (TDRM) method to calculate anisotropy parameters for positive and negative sidebands of selected harmonics generated by two-color two-photon above-threshold ionization of argon. We consider odd harmonics of an 800-nm field ranging from the 13th to 19th harmonic, overlapped by a fundamental 800-nm IR field. The anisotropy parameters obtained using the TDRM method are compared with those obtained using a second-order perturbation theory with a model potential approach and a soft photon approximation approach. Where available, a comparison is also made to published experimental results. All three theoretical approaches provide similar values for anisotropy parameters. The TDRM approach obtains values that are closest to published experimental values. At high photon energies, the differences between each of the theoretical methods become less significant.

Autoecological Approaches to Resolve Subjective Taxonomic Divisions within Arcellacea

Arcellacea (testate lobose amoebae) are important lacustrine environmental indicators that have been used in paleoclimatic reconstructions, assessing the effectiveness of mine tailings pond reclamation projects and for studying the effects of land use change in rural, industrial and urban settings. Recognition of ecophenotypically significant infra-specific ‘strains’ within arcellacean assemblages has the potential to enhance the utility of the group in characterizing contemporary and paleoenvironments. We present a novel approach which employs statistical tools to investigate the environmental and taxonomic significance of proposed strains. We test this approach on two identified strains: Difflugia protaeiformis Lamarck strain ‘acuminata’ (DPA), characterized by fine grained agglutination, and Difflugia protaeiformis Lamarck strain ‘claviformis’ (DPC), characterized by coarse grained agglutination. Redundancy analysis indicated that both organisms are associated with similar environmental variables. No relationship was observed between substrate particle size and abundance of DPC, indicating that DPC has a size preference for xenosomes during test construction. Thus DPC should not be designated as a distinct strain but rather form a species complex with DPA. This study elucidates the need to justify the designation of strains based on their autecology in addition to morphological stability.

Phylogeographical analysis of two cold-tolerant plants with disjunct Lusitanian distributions does not support in situ survival during the last glaciation

Aim: We used a combination of modelling and genetic approaches to investigate whether Pinguicula grandiflora and Saxifraga spathularis, two species that exhibit disjunct Lusitanian distributions, may have persisted through the Last Glacial Maximum (LGM, c. 21 ka) in separate northern and southern refugia.

Location: Northern and eastern Spain and south-western Ireland.

Methods: Palaeodistribution modelling using maxent was used to identify putative refugial areas for both species at the LGM, as well as to estimate their distributions during the Last Interglacial (LIG, c. 120 ka). Phylogeographical analysis of samples from across both species' ranges was carried out using one chloroplast and three nuclear loci for each species.

Results: The palaeodistribution models identified very limited suitable habitat for either species during the LIG, followed by expansion during the LGM. A single, large refugium across northern Spain and southern France was postulated for P. grandiflora. Two suitable regions were identified for S. spathularis: one in northern Spain, corresponding to the eastern part of the species' present-day distribution in Iberia, and the other on the continental shelf off the west coast of Brittany, south of the limit of the British–Irish ice sheet. Phylogeographical analyses indicated extremely reduced levels of genetic diversity in Irish populations of P. grandiflora relative to those in mainland Europe, but comparable levels of diversity between Irish and mainland European populations of S. spathularis, including the occurrence of private hapotypes in both regions.

Main conclusions: Modelling and phylogeographical analyses indicate that P. grandiflora persisted through the LGM in a southern refugium, and achieved its current Irish distribution via northward dispersal after the retreat of the ice sheets. Although the results for S. spathularis are more equivocal, a similar recolonization scenario also seems the most likely explanation for the species' current distribution.

Two Trilogies:On Stewart Parker and Tom Murphy

This chapter discusses the relations between Irish cinema and the other arts- chiefly, literature, theatre, painting, and photography. It provides a critical overview of the main scholarly approaches to those forms of adaptation and citation that have tended to dominate Irish film production. It argues that factors such as the historic marginalization of non-literary modernist art in Ireland, a deep cultural resistance to intellectual and politically-engaged filmmaking, and a commercially-driven attachment to formulaic narrative structures, are among the reasons why Ireland has generally failed to produce a distinctive and successful cinema. The chapter concludes by discussing some films that have resisted this trend by offering their audiences a more creative approach to -- or poetics of -- adaptation that has more in common with the visual -- rather than literary -- arts in Ireland.

ARTICLE: Anarchy and International Law: The Approaches of Hedley Bull and Noam Chomsky

Are anarchy and the law antithetical? Not so, as for more than 350 years international law has governed a legal order based on anarchy; wherein no central authority exists and law functions not on the basis of coercion but on cooperation whereby States must agree to each specific laws before it is bound by its obligations. This article contemplates two manners in which an anarchist might consider international law interesting: first, as a legal system which governs an anarchical society as described by Hedley Bull in line with the English School of International Relations; and second, as a manifestation of a State system which, though illegitimate can be utilized, as Noam Chomsky does, for tactical reasons to demonstrate its inconsistencies and thus weakening the system with the ultimate aim being its implosion

Convergence of products from Povarov and von Miller reactions: approaches to helquinoline

Yttrium triflate or triflic acid catalysed Povarov reaction of methyl anthranilate with ethyl vinyl ether, both as aldehyde surrogate and as alkene, gave the desired 2-methyl-4-ethoxytetrahydroquinoline diastereoisomers as the major products along with four component coupling von Miller adducts. A proton NMR-study, using yttrium triflate as catalyst, revealed that the cis-diastereoisomers were the initial major products in both the Povarov and von Miller reactions but that these isomerised to the trans-diastereoisomers under the reaction conditions. Two distinct pathways for forming von Miller adducts were uncovered with the initial Povarov products being converted to von Miller adducts under the reaction conditions. Replacement of the 4-ethoxy with a 4-methoxy group under acidic conditions gave predominantly the trans-diastereoisomer, which was subsequently converted to a cis/trans mixture of the tetrahydroquinoline antibiotic helquinoline. It was also possible to convert the von Miller products to Povarov products under acidic conditions

Two-Stage Orthogonal Least Squares Methods for Neural Network Construction

A number of neural networks can be formulated as the linear-in-the-parameters models. Training such networks can be transformed to a model selection problem where a compact model is selected from all the candidates using subset selection algorithms. Forward selection methods are popular fast subset selection approaches. However, they may only produce suboptimal models and can be trapped into a local minimum. More recently, a two-stage fast recursive algorithm (TSFRA) combining forward selection and backward model refinement has been proposed to improve the compactness and generalization performance of the model. This paper proposes unified two-stage orthogonal least squares methods instead of the fast recursive-based methods. In contrast to the TSFRA, this paper derives a new simplified relationship between the forward and the backward stages to avoid repetitive computations using the inherent orthogonal properties of the least squares methods. Furthermore, a new term exchanging scheme for backward model refinement is introduced to reduce computational demand. Finally, given the error reduction ratio criterion, effective and efficient forward and backward subset selection procedures are proposed. Extensive examples are presented to demonstrate the improved model compactness constructed by the proposed technique in comparison with some popular methods.

Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica

Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member.

Risk, Recovery and Capacity: Competing or Complementary Approaches to Mental Health Social Work

Mental health social workers have a central role in providing support to people with mental health problems and in the use of coercion aimed at dealing with risk. Mental health services have traditionally focused on monitoring symptoms and ascertaining the risks people may present to themselves and/or others. This well-intentioned but negative focus on deficits has contributed to stigma, discrimination and exclusion experienced by service users. Emerging understandings of risk also suggest that our inability to accurately predict the future makes risk a problematic foundation for compulsory intervention. It is therefore argued that alternative approaches are needed to make issues of power and inequality transparent. This article focuses on two areas of practice: the use of recovery based approaches, which promote supported decision making and inclusion; and the assessment of a person’s ability to make decisions, their mental capacity, as a less discriminatory gateway criterion than risk for compulsory intervention.

Bright Molecules for Sensing, Computing and Imaging: A Tale of Two Once-troubled Cities

The circumstances in Colombo, Sri Lanka, and in Belfast, Northern Ireland, which led to a) the generalization of luminescent PET (photoinduced electron transfer) sensing/switching as a design tool, b) the construction of a market-leading blood electrolyte analyzer and c) the invention of molecular logic-based computation as an experimental field, are delineated. Efforts to extend the philosophy of these approaches into issues of small object identification, nanometric mapping, animal visual perception and visual art are also outlined.

Asthma control and exacerbations: two different sides of the same coin.

Purpose of review: Optimal asthma management includes both the control of asthma symptoms and reducing the risk of future asthma exacerbations. Traditionally, treatment has been adjusted largely on the basis of symptoms and lung function and for many patients, this approach delivers both excellent symptom control and reduced risk. However, the relationship between these two key components of the disease may vary between different asthmatic phenotypes and disease severities and there is increasing recognition of the need for more individualized treatment approaches.

Recent findings: A number of factors which predict exacerbation risk have been identified including demographic and behavioural features and specific inflammatory biomarkers. Type-2 cytokine-driven eosinophilic airways inflammation predisposes to frequent exacerbations and predicts response to corticosteroids, and the usefulness of sputum eosinophilia as both a marker of exacerbation risk and biomarker for adjustment of corticosteroid treatment has been established for some time. However, attempts to develop surrogate markers, which would be more straightforward to deliver in the clinic, have been challenging.

Summary: Some patients with asthma have persistent symptoms in the absence of type-2 cytokine driven-eosinophilic airways inflammation due to noncorticosteroid responsive mechanisms (T2-low disease). Composite biomarker strategies using easily measured surrogate indicators of type-2 inflammation (such as fractional exhaled nitric oxide, blood eosinophil count and serum periostin levels) may predict exacerbation risk better but it is unclear if they can be used to adjust corticosteroid treatment. Biomarkers will be used to target novel biologic treatments but additionally may be used to optimize corticosteroid treatment dose and act as prognostics for exacerbation risk and potentially other important longer term asthma outcomes.