A survey of sidedness in Northern Irish schoolchildren: The interaction of sex, age, and task

The study examined lateral preference in use of hands, feet, eyes, and ears in a group of nearly 5000 schoolchildren in Northern Ireland. Performance tests were carried out by student teachers during their school-based work in 2002 and data were submitted on-line. Six tasks were used-writing, throwing a ball, kicking a ball, hopping, listening to quiet sounds, and looking through a cardboard tube. There was right bias in every task but the extent of it differed between tasks. Males were generally less right biased than females, and younger children less than older ones; for hearing, the changes with age were markedly different in the two sexes, with females showing a strong increase in right bias but males showing none. These observational results do little to illuminate the reasons for the patterns observed.

Simulated predator extinctions: Predator identity affects survival and recruitment of oysters

The rate of species loss is increasing at a global scale, and human-induced extinctions are biased toward predator species. We examined the effects of predator extinctions on a foundation species, the eastern oyster (Crassostrea virginica). We performed a factorial experiment manipulating the presence and abundance of three of the most common predatory crabs, the blue crab (Callinectes sapidus), stone crab (Menippe mercenaria), and mud crab (Panopeus herbstii) in estuaries in the eastern United States. We tested the effects of species richness and identity of predators on juvenile oyster survival, oyster recruitment, and organic matter content of sediment. We also manipulated the density of each of the predators and controlled for the loss of biomass of species by maintaining a constant mass of predators in one set of treatments and simultaneously using an additive design. This design allowed us to test the density dependence of our results and test for functional compensation by other species. The identity of predator species, but not richness, affected oyster populations. The loss of blue crabs, alone or in combination with either of the other species, affected the survival rate of juvenile oysters. Blue crabs and stone crabs both affected oyster recruitment and sediment organic matter negatively. Mud crabs at higher than ambient densities, however, could fulfill some of the functions of blue and stone crabs, suggesting a level of ecological redundancy. Importantly, the strong effects of blue crabs in all processes measured no longer occurred when individuals were present at higher-than-ambient densities. Their role as dominant predator is, therefore, dependent on their density within the system and the density of other species within their guild (e.g., mud crabs). Our findings support the hypothesis that the effects of species loss at higher trophic levels are determined by predator identity and are subject to complex intraguild interactions that are largely density dependent. Understanding the role of biodiversity in ecosystem functioning or addressing practical concerns, such as loss of predators owing to overharvesting, remains complicated because accurate predictions require detailed knowledge of the system and should be drawn from sound experimental evidence, not based on observations or generalized models.

Resolving questions about bias in real and hypothetical referenda

Despite 10 years of research on behavior in hypothetical referenda, conflict remains in the literature on whether or not the mechanism generates biased responses compared to real referenda, and the nature and source of any such bias. Almost all previous inquiry in respect of this issue has concentrated on bias at the aggregate level. This paper reports a series of three experiments which focuses on bias at the individual level and how this can translate to bias at the aggregate level. The authors argue that only an individual approach to hypothetical bias is consistent with the concept of incentive compatibility. The results of these experiments reflect these previous conflicting findings but go on to show that individual hypothetical bias is a robust result driven by the differing influence of pure self-interest and other-regarding preferences in real and hypothetical situations, rather than by a single behavioral theory such as free riding. In a hypothetical situation these preferences cause yea-saying and non-demand revealing voting. This suggests that investigation of individual respondents in other hypothetical one-shot binary choices may also provide us with insights into aggregate behavior in these situations.

An Empirical Analysis of Scale and Scope Economies and Technical Change in an Irish Multiproduct Banking Firm

In contrast to most empirical investigations of the efficiency of multiproduct financial institutions, which either estimate scale and scope economies with a given state of technology, or only analyse technical change in the presence of overall scale economies, this study estimates overall scale economies, product-specific scale economies and scope economies in the presence of both neutral and non-neutral technical change. Also, in contrast to most other empirical studies in this area, standard errors are computed for all relevant statistics. The findings indicate diseconomies of scope; overall diseconomies of scale; product-specific economies are decreasing for investments and increasing for loans; in addition to substantial neutral technical change, biased technical change is labour- and capital-saving and deposits-using in character.

How do grazers achieve their distribution? A continuum of models from random diffusion to the ideal free distribution using biased random walks

A conceptual model is described for generating distributions of grazing animals, according to their searching behavior, to investigate the mechanisms animals may use to achieve their distributions. The model simulates behaviors ranging from random diffusion, through taxis and cognitively aided navigation (i.e., using memory), to the optimization extreme of the Ideal Free Distribution. These behaviors are generated from simulation of biased diffusion that operates at multiple scales simultaneously, formalizing ideas of multiple-scale foraging behavior. It uses probabilistic bias to represent decisions, allowing multiple search goals to be combined (e.g., foraging and social goals) and the representation of suboptimal behavior. By allowing bias to arise at multiple scales within the environment, each weighted relative to the others, the model can represent different scales of simultaneous decision-making and scale-dependent behavior. The model also allows different constraints to be applied to the animal's ability (e.g., applying food-patch accessibility and information limits). Simulations show that foraging-decision randomness and spatial scale of decision bias have potentially profound effects on both animal intake rate and the distribution of resources in the environment. Spatial variograms show that foraging strategies can differentially change the spatial pattern of resource abundance in the environment to one characteristic of the foraging strategy.</

Red-shifts and red herrings in geographical ecology

I draw attention to the need for ecologists to take spatial structure into account more seriously in hypothesis testing. If spatial autocorrelation is ignored, as it usually is, then analyses of ecological patterns in terms of environmental factors can produce very misleading results. This is demonstrated using synthetic but realistic spatial patterns with known spatial properties which are subjected to classical correlation and multiple regression analyses. Correlation between an autocorrelated response variable and each of a set of explanatory variables is strongly biased in favour of those explanatory variables that are highly autocorrelated - the expected magnitude of the correlation coefficient increases with autocorrelation even if the spatial patterns are completely independent. Similarly, multiple regression analysis finds highly autocorrelated explanatory variables "significant" much more frequently than it should. The chances of mistakenly identifying a "significant" slope across an autocorrelated pattern is very high if classical regression is used. Consequently, under these circumstances strongly autocorrelated environmental factors reported in the literature as associated with ecological patterns may not actually be significant. It is likely that these factors wrongly described as important constitute a red-shifted subset of the set of potential explanations, and that more spatially discontinuous factors (those with bluer spectra) are actually relatively more important than their present status suggests. There is much that ecologists can do to improve on this situation. I discuss various approaches to the problem of spatial autocorrelation from the literature and present a randomisation test for the association of two spatial patterns which has advantages over currently available methods.

Distinct CCK-2 Receptor Conformations Associated with β-Arrestin-2 Recruitment or Phospholipase-C Activation Revealed by a Biased Antagonist

Seven-transmembrane receptors (7TMRs), also termed G protein-coupled receptors (GPCRs), form the largest class of cell surface membrane receptors, involving several hundred members in the human genome. Near 30% of marketed pharmacological agents target 7TMRs. 7TMRs adopt multiple conformations upon agonist binding. Biased agonists, in contrast to non-biased agonists, are believed to stabilize conformations preferentially activating either G-protein- or ß-arrestin-dependent signalling pathways. However, proof that cognate conformations of receptors display structural differences within their binding site where biased agonism initiates, are still lacking. Here, we show that a non-biased agonist, cholecystokinin (CCK) induces conformational states of the CCK2R activating Gq-protein-dependent pathway (CCK2RG) or recruiting ß-arrestin2 (CCK2Rß) that are pharmacologically and structurally distinct. Two structurally unrelated antagonists competitively inhibited both pathways. A third ligand (GV150,013X), acted as a high affinity competitive antagonist on CCK2RG but was nearly inefficient as inhibitor of CCK2Rß. Several structural elements on both GV150,013X and in CCK2R binding cavity, which hinder binding of GV150,013X only to the CCK2Rß were identified. At last, proximity between two conserved amino acids from transmembrane helices 3 and 7 interacting through sulphur-aromatic interaction was shown to be crucial for selective stabilization of the CCK2Rß state. These data establish structural evidences for distinct conformations of a 7TMR associated with ß-arrestin-2 recruitment or G-protein coupling and validate relevance of the design of biased ligands able to selectively target each functional conformation of 7TMRs.

Independent and Interdependent Immunoregulatory Effects of IL-27, IFN-β, and IL-10 in the Suppression of Human Th17 Cells and Murine Experimental Autoimmune Encephalomyelitis

IFN-ß, IL-27, and IL-10 have been shown to exert a range of similar immunoregulatory effects in murine and human experimental systems, particularly in Th1- and Th17-mediated models of autoimmune inflammatory disease. In this study we sought to translate some of our previous findings in murine systems to human in vitro models and delineate the interdependence of these different cytokines in their immunoregulatory effects. We demonstrate that human IL-27 upregulates IL-10 in T cell-activated PBMC cultures and that IFN-ß drives IL-27 production in activated monocytes. IFN-ß-driven IL-27 is responsible for the upregulation of IL-10, but not IL-17 suppression, by IFN-ß in human PBMCs. Surprisingly, IL-10 is not required for the suppression of IL-17 by either IL-27 or IFN-ß in this model or in de novo differentiating Th17 cells, nor is IL-27 signaling required for the suppression of experimental autoimmune encephalomyelitis (EAE) by IFN-ß in vivo. Furthermore, and even more surprisingly, IL-10 is not required for the suppression of Th17-biased EAE by IL-27, in sharp contrast to Th1-biased EAE. In conclusion, IFN-ß and IL-27 both induce human IL-10, both suppress human Th17 responses, and both suppress murine EAE. However, IL-27 signaling is not required for the therapeutic effect of IFN-ß in EAE. Suppression of Th17-biased EAE by IL-27 is IL-10-independent, in contrast to its mechanism of action in Th1-biased EAE. Taken together, these findings delineate a complex set of interdependent and independent immunoregulatory mechanisms of IFN-ß, IL-27, and IL-10 in human experimental models and in murine Th1- and Th17-driven autoimmunity.

A self-learning algorithm for biased molecular dynamics

A new self-learning algorithm for accelerated dynamics, reconnaissance metadynamics, is proposed that is able to work with a very large number of collective coordinates. Acceleration of the dynamics is achieved by constructing a bias potential in terms of a patchwork of one-dimensional, locally valid collective coordinates. These collective coordinates are obtained from trajectory analyses so that they adapt to any new features encountered during the simulation. We show how this methodology can be used to enhance sampling in real chemical systems citing examples both from the physics of clusters and from the biological sciences.

Simulations of Biased Agonists in the β2 Adrenergic Receptor with Accelerated Molecular Dynamics

The biased agonism of the G protein-coupled receptors (GPCRs), where in addition to a traditional G protein-signalling pathway a GPCR promotes intracellular signals though ß-arrestin, is a novel paradigm in pharmacology. Biochemical and biophysical studies have suggested that a GPCR forms a distinct ensemble of conformations signalling through the G protein and ß-arrestin. Here we report on the dynamics of the ß2 adrenergic receptor bound to the ß-arrestin and G protein biased agonists and the empty receptor to further characterize the receptor conformational changes caused by biased agonists. We use conventional and accelerated molecular dynamics (aMD) simulations to explore the conformational transitions of the GPCR from the active state to the inactive state. We found that aMD simulations enable monitoring the transition within the nanosecond timescale while capturing the known microscopic characteristics of the inactive states, such as the ionic lock, the inward position of F6.44, and water clusters. Distinct conformational states are shown to be stabilized by each biased agonist. In particular, in simulations of the receptor with the ß-arrestin biased agonist, N-cyclopentylbutanepherine we observe a different pattern of motions in helix 7 when compared to simulations with the G protein biased agonist, Salbutamol that involves perturbations of the network of interactions within the NPxxY motif. Understanding the network of interactions induced by biased ligands and the subsequent receptor conformational shifts will lead to development of more efficient drugs. © 2013 American Chemical Society

Knowledge work: Gender-blind or gender-biased?

Knowledge-intensive firms (KIFs) have been the subject of growing interest from researchers. However, investigations into the comparative experiences of men and women in KIFs remain sparse, and little is known about women's participation in the processes of innovation and knowledge exchange and combination that are core features of KIFs. The article reports on the findings of a study in the UK and Ireland involving 498 male and female knowledge workers in KIFs. Despite equal levels of qualification and experience, women are more likely to be in lower status and less secure jobs. They also predominantly occupy roles featuring less variety and autonomy than men and, despite comparable levels of knowledge exchange and combination, are less likely to be in a position to translate this into the innovative work behaviours necessary for career advancement. The findings suggest that women's experiences of and participation in knowledge processes within KIFs differ fundamentally from men's. © The Author(s) 2012.

The value of water quality improvements in the region Berlin-Brandenburg as a function of distance and state residency

This study uses a discrete choice experiment (DCE) to elicit willingness to pay estimates for changes in the water quality of three rivers. As many regions the metropolitan region Berlin-Brandenburg struggles to achieve the objectives of the Water Framework Directive until 2015. A major problem is the high load of nutrients. As the region is part of two states (Länder) and the river sections are common throughout the whole region we account for the spatial context twofold. Firstly, we incorporate the distance between each respondent and all river stretches in all MNL and RPL models, and, secondly, we consider whether respondents reside in the state of Berlin or Brandenburg. The compensating variation (CV) calculated for various scenarios shows that overall people would significantly benefit from improved water quality. The CV measures, however, also reveal that not considering the spatial context would result in severely biased welfare measures. While the distance decay effect lowers CV, state residency is connected to the frequency of status quo choices and not accounting for residency would underestimate possible welfare gains in one state. Another finding is that the extent of the market varies with respect to attributes (river stretches) and attribute levels (water quality levels).

Pulsed second harmonic generation by stacks of magnetically biased semiconductor layers

The pulsed second harmonic generation (SHG) by periodic stacks of nonlinear semiconductor layers with external magnetic bias has been studied in the self-consistent problem formulation, taking into account mobility of carriers. The products of nonlinear scattering in the three-wave mixing process are examined. It is demonstrated that the waveform evolution in magnetoactive weakly nonlinear semiconductor periodic structure illuminated by Gaussian pulse is strongly affected by the magnetic bias and collision frequency of the carriers. The effect of nonreciprocity on the SHG efficiency is discussed and illustrated by the examples. © 2013 European Microwave Association.

The Kremlin's Scholar. A Memoir of Soviet Politics under Stalin and Khrushchev

The memoirs are dominated by two grand figures of Soviet history, Stalin and Khrushchev. The account of Stalin is riddled with ambiguities. There is an undoubted personal admiration for Stalin, his intellectual and political capacity (Stalin allegedly read 300 pages per day), his simplicity in daily life seen in "an old tunic, patched-up socks, almost constant isolation" (p. 190). At the same time, Shepilov acknowledged the paranoid aspects of Stalin's personality, especially towards the end of his life. Stalin's mechanisms of power are illustrated by Shepilov's account of work on a new book on political economy. Stalin personally chose key people for important tasks and controlled them at key junctures to ensure the desired outcome. In this light, Shepilov's claims that the Great Purges of the late 1930s could have been outside of Stalin's immediate control seem implausible, to say the least (p. 41).

All Stalin's deficiencies, however, pale in comparison with those of Khrushchev, the bête noire of Shepilov's memoirs. There is plenty of criticism of Khrushchev's policies, particularly in agriculture and foreign affairs. What comes across most pungently is, however, Shepilov's disdain of Khrushchev's personality and leadership style. In this respect, the book is unashamedly biased and remarkable for its omissions as much as for its revelations.

Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease: Results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES)

Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single ‘baseline’ measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (≥25–<30 kg/m2) or moderately obese (≥30–<35) tended to be associated with a lower risk of mortality compared to normal (≥18.5–<25): ESTHER, HR (95 % CI) 0.69 (0.58–0.82) and 0.78 (0.63–0.97); Rotterdam, 0.86 (0.79–0.94) and 0.80 (0.72–0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95 % CI) 0.88 (0.76–1.02); and moderately obese in Tromsø, HR (95 % CI) 0.79 (0.62–1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity.