The influence of hypercapnia and the infaunal brittlestar <i>Amphiura filiformis</i> on sediment nutrient flux – will ocean acidification affect nutrient exchange?

Rising levels of atmospheric carbon dioxide and the concomitant increased uptake of this by the oceans is resulting in hypercapnia-related reduction of ocean pH. Research focussed on the direct effects of these physicochemical changes on marine invertebrates has begun to improve our understanding of impacts at the level of individual physiologies. However, CO₂-related impairment of organisms' contribution to ecological or ecosystem processes has barely been addressed. The burrowing ophiuroid <i>Amphiura filiformis</i>, which has a physiology that makes it susceptible to reduced pH, plays a key role in sediment nutrient cycling by mixing and irrigating the sediment, a process known as bioturbation. Here we investigate the role of <i>A. filiformis</i> in modifying nutrient flux rates across the sediment-water boundary and the impact of CO₂- related acidification on this process. A 40 day exposure study was conducted under predicted pH scenarios from the years 2100 (pH 7.7) and 2300 (pH 7.3), plus an additional treatment of pH 6.8. This study demonstrated strong relationships between <i>A. filiformis</i> density and cycling of some nutrients; <iA. filiformis</i> activity increases the sediment uptake of phosphate and the release of nitrite and nitrate. No relationship between <i>A. filiformis</i> density and the flux of ammonium or silicate were observed. Results also indicated that, within the timescale of this experiment, effects at the individual bioturbator level appear not to translate into reduced ecosystem influence. However, long term survival of key bioturbating species is far from assured and changes in both bioturbation and microbial processes could alter key biogeochemical processes in future, more acidic oceans

Heterokairy: a significant form of developmental plasticity?

There is a current surge of research interest in the potential role of developmental plasticity in adaptation and evolution. Here we make a case that some of this research effort should explore the adaptive significance of heterokairy, a specific type of plasticity that describes environmentally driven, altered timing of development within a species. This emphasis seems warranted given the pervasive occurrence of heterochrony, altered developmental timing between species, in evolution. We briefly review studies investigating heterochrony within an adaptive context across animal taxa, including examples that explore links between heterokairy and heterochrony. We then outline how sequence heterokairy could be included within the research agenda for developmental plasticity. We suggest that the study of heterokairy may be particularly pertinent in (i) determining the importance of non-adaptive plasticity, and (ii) embedding concepts from comparative embryology such as developmental modularity and disassociation within a developmental plasticity framework

Adaptation and acclimatization to ocean acidification in marine ectotherms: an in situ transplant experiment with polychaetes at a shallow CO₂ vent system

Metabolic rate determines the physiological and life-history performances of ectotherms. Thus, the extent to which such rates are sensitive and plastic to environmental perturbation is central to an organism's ability to function in a changing environment. Little is known of long-term metabolic plasticity and potential for metabolic adaptation in marine ectotherms exposed to elevated pCO₂. Consequently, we carried out a series of in situ transplant experiments using a number of tolerant and sensitive polychaete species living around a natural CO₂ vent system. Here, we show that a marine metazoan (i.e. Platynereis dumerilii) was able to adapt to chronic and elevated levels of pCO₂. The vent population of P. dumerilii was physiologically and genetically different from nearby populations that experience low pCO₂, as well as smaller in body size. By contrast, different populations of Amphiglena mediterranea showed marked physiological plasticity indicating that adaptation or acclimatization are both viable strategies for the successful colonization of elevated pCO₂ environments. In addition, sensitive species showed either a reduced or increased metabolism when exposed acutely to elevated pCO₂. Our findings may help explain, from a metabolic perspective, the occurrence of past mass extinction, as well as shed light on alternative pathways of resilience in species facing ongoing ocean acidification

Photoemission studies of high temperature superconductors

Photoemission studies have been performed on all classes of high temperature superconductors except the Tl‐related compounds. Particular attention was paid to the surface cleanliness. Comparison with band calculation shows that the one‐electron picture cannot adequately explain the electronic structure of this type of materials. Most important, Cu satellites were observed both in the valence band and the Cu 2p core level for all the samples studied, signaling the importance of the d‐d correlation effects. the Cu 3d character of these satellites in the valence band was verified using resonance photoemission. The results have been interpreted in terms of a cluster model derived from the two band Anderson Hamiltonian, which in the past has been used successfully to describe the electronic structure of highly correlated systems. No clear satellite structure was observed in the O 1s core spectrum, which is consistent with the band‐like nature of the oxygen states. Examples of changes in the electronic structure, which could be related to Tc, (such as substituting Y by Pr in the Y‐Ba‐Cu‐O system and altering the number of Cu‐O layers in the Bi‐Ca‐Sr‐Cu‐O system), are also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87348/2/330_1.pd

Higher analogues of the discrete-time Toda equation and the quotient-difference algorithm

The discrete-time Toda equation arises as a universal equation for the relevant Hankel determinants associated with one-variable orthogonal polynomials through the mechanism of adjacency, which amounts to the inclusion of shifted weight functions in the orthogonality condition. In this paper we extend this mechanism to a new class of two-variable orthogonal polynomials where the variables are related via an elliptic curve. This leads to a `Higher order Analogue of the Discrete-time Toda' (HADT) equation for the associated Hankel determinants, together with its Lax pair, which is derived from the relevant recurrence relations for the orthogonal polynomials. In a similar way as the quotient-difference (QD) algorithm is related to the discrete-time Toda equation, a novel quotient-quotient-difference (QQD) scheme is presented for the HADT equation. We show that for both the HADT equation and the QQD scheme, there exists well-posed $s$-periodic initial value problems, for almost all \s\in\Z^2. From the Lax-pairs we furthermore derive invariants for corresponding reductions to dynamical mappings for some explicit examples.Comment: 38 page

Soft X-ray analysis of a loop flare on the Sun

We present the results of an analysis of soft X-ray images for a solar flare which occurred on 1992 July 11. This flare, as seen in Yohkoh Soft X-ray Telescope (SXT) images was of comparatively simple geometry, consisting of two bright footpoints early in the flare with a bright loop seen later in the flare. We examine how closely this flare compares with the supposed paradigm of a confined simple-loop flare. Closer examination of the SXT images reveals that the flare structure consisted of at least two adjacent loops, one much fainter than the other. We examine the brighter of the two soft X-ray loops. The SXT images reveal an apparent slow, northward motion of this loop (roughly transverse to its major axis). Examination of derived emission measure and temperature images also indicate an apparent northward motion. In addition, we find an increase in the cross-sectional width at the top of the loop with time. Emission measure maps derived from the SXT images also indicates an apparent broadening of the loop-top region. We infer that the apparent northward motion and the apparent broadening of the soft X-ray emission can be explained in a reconnection scenario where successive magnetic field structures do not lie in a plane but are tilted to the south of the line of sight but with successively brightening loops oriented at less tilted angles. Halpha images for this flare reveal an evolution from a few brilliant points to a short two- ribbon-like appearance. Comparison of the SXT images with the Halpha images shows that the Halpha patches are aligned with the footpoints of the soft X-ray loops, suggesting the presence of a small arcade structure. There is no clear evidence for an eruptive signature in our observations nor in reports from other observations. The lack of an eruptive signature could suggest that the flare may have been a confined simple-loop flare, but this is not compelling due to a gap in the coronal observations prior to and early in the event. Analysis of our observations indicate that the flare exhibited characteristics suggesting that it may be better understood as a mini-arcade flare. These results casts doubt on the validity of the supposed paradigm of a confined simple-loop flare, at least for this flare. They indicate that even an apparently simple-loop flare may be considered to be a variety of arcade flare. We also find an effect which, to our knowledge, has not been reported before: the hot flaring regions later become cooler than the surrounding quiescent corona. That is, the flare loops do not evolve into bright active region loops, but into cooler loops. This may indicate an increase in the efficiency of the cooling mechanism or a transformed equilibrium state within the flaring loops

Strain‐Promoted Cycloadditions in Lipid Bilayers Triggered by Liposome Fusion

Due to the variety of roles served by the cell membrane, its composition and structure are complex, making it difficult to study. Bioorthogonal reactions, such as the strain promoted azide-alkyne cycloaddition (SPAAC), are powerful tools for exploring the function of biomolecules in their native environment but have been largely unexplored within the context of lipid bilayers. Here, we developed a new approach to study the SPAAC reaction in liposomal membranes using azide- and strained alkyne-functionalized Förster resonance energy transfer (FRET) dye pairs. This study represents the first characterization of the SPAAC reaction between diffusing molecules inside liposomal membranes. Potential applications of this work include in situ bioorthogonal labeling of membrane proteins, improved understanding of membrane dynamics and fluidity, and the generation of new probes for biosensing assays

Phase 1 dose-escalation study of S-222611, an oral reversible dual tyrosine kinase inhibitor of EGFR and HER2, in patients with solid tumours.

BACKGROUND: S-222611 is a reversible inhibitor of EGFR, HER2 and HER4 with preclinical activity in models expressing these proteins. We have performed a Phase 1 study to determine safety, maximum tolerated dose (MTD), pharmacokinetic profile (PK) and efficacy in patients with solid tumours expressing EGFR or HER2. PATIENTS AND METHODS: Subjects had advanced tumours not suitable for standard treatment, expressing EGFR or HER2, and/or with amplified HER2. Daily oral doses of S-222611 were escalated from 100mg to 1600 mg. Full plasma concentration profiles for drug and metabolites were obtained. RESULTS: 33 patients received S-222611. It was well tolerated, and the most common toxicities, almost all mild (grade 1 or 2), were diarrhoea, fatigue, rash and nausea. Only two dose-limiting toxicities occurred (diarrhoea and rash), which resolved on interruption. MTD was not reached. Plasma exposure increased with dose up to 800 mg, exceeding levels eliciting pre-clinical responses. The plasma terminal half-life was more than 24h, supporting once daily dosing. Responses were seen over a wide range of doses in oesophageal, breast and renal tumours, including a complete clinical response in a patient with HER2-positive breast carcinoma previously treated with lapatinib and trastuzumab. Four patients have remained on treatment for more than 12 months. Downregulation of pHER3 was seen in paired tumour biopsies from a responding patient. CONCLUSIONS: Continuous daily oral S-222611 is well tolerated, modulates oncogenic signalling, and has significant antitumour activity. The recommended Phase 2 dose, based on PK and efficacy, is 800 mg/day.The authors acknowledge financial support from the UK Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust (and NIHR Clinical Research Facility), and to The University of Cambridge and Cambridge University Hospital NHS Foundation Trust. Cambridge, King’s College London, and Newcastle are Experimental Cancer Medicine Centres.This is the accepted manuscript. The final version is available from http://www.sciencedirect.com/science/article/pii/S0959804914010922

Women and Illegal Activities: Gender Differences and Women's Willingness to Comply Over Time

In recent years the topics of illegal activities such as corruption or tax evasion have attracted a great deal of attention. However, there is still a lack of substantial empirical evidence about the determinants of compliance. The aim of this paper is to investigate empirically whether women are more willing to be compliant than men and whether we observe (among women and in general) differences in attitudes among similar age groups in different time periods (cohort effect) or changing attitudes of the same cohorts over time (age effect) using data from eight Western European countries from the World Values Survey and the European Values Survey that span the period from 1981 to 1999. The results reveal higher willingness to comply among women and an age rather than a cohort effect. Working Paper 06-5