New direct payments scheme: targeting and redistribution in the future CAP

The Commission has proposed that a revised version of the present regime of direct payments should be rolled forward into the post-2013 CAP. There would be a limited redistribution of funds between Member States. Thirty per cent of the budget would be allocated to a new greening component, which would be problematic in the WTO. Non-active farmers would not qualify for aid; and payments would be capped. Special schemes would be introduced for small farmers, for young new entrants, and for disadvantaged regions.

Synthesis and biological in vitro evaluation of novel PEG-psoralen conjugates

Psoralens are well-known photosensitizers, and 8- methoxypsoralen and 4,5',8-trimethylpsoralen are widely used in photomedicine as "psoralens plus UVA therapy" (PUVA), in photopheresis, and in sterilization of blood preparations. In an attempt to improve the therapeutic efficiency of PUVA therapy and photopheresis, four poly(ethylene glycol) (PEG)-psoralen conjugates were synthesized to promote tumor targeting by the enhanced permeability and retention (EPR) effect. Peptide linkers were used to exploit specific enzymatic cleavage by lysosomal proteases. A new psoralen, 4-hydroxymethyl-4', 8-dimethylpsoralen (6), suitable for polymer conjugation was synthesized. The hydroxy group allowed exploring different strategies for PEG conjugation, and linkages with different stability such ester or urethanes were obtained. PEG (5 kDa) was covalently conjugated to the new psoralen derivative using four different linkages, namely, (i) direct ester bond (7), (ii) ester linkage with a peptide spacer (8), (iii) a carbamic linker (9), and (iv) a carbamic linker with a peptide spacer (12). The stability of these new conjugates was assessed at different pHs, in plasma and following incubation with cathepsin B. Conjugates 7 and 8 were rapidly hydrolyzed in plasma, while 9 was stable in buffer and in the presence of cathepsin B. As expected, only the conjugates containing the peptide linker released the drug in presence of cathepsin B. In vitro evaluation of the cytotoxic activity in the presence and absence of light was carried out in two cell lines (MCF-7 and A375 cells). Conjugates 7 and 8 displayed a similar activity to the free drug (probably due to the low stability of the ester linkage). Interestingly, the conjugates containing the carbamate linkage (9 and 12) were completely inactive in the dark (IC50 > 100 mu M in both cell lines). However, antiproliferative activity become apparent after UV irradiation. Conjugate 12 appears to be the most promising for future in vivo evaluation, since it was relatively stable in plasma, which should allow tumor targeting and drug release to occur by cathepsin B-mediated hydrolysis.

Protease-activated receptor 2: activation, signalling and function

PARs (protease-activated receptors) are a family of four G-protein-coupled receptors for proteases from the circulation, inflammatory cells and epithelial tissues. This report focuses on PAR(2), which plays an important role in inflammation and pain. Pancreatic (trypsin I and II) and extrapancreatic (trypsin IV) trypsins, mast cell tryptase and coagulation factors VIIa and Xa cleave and activate PAR(2). Proteases cleave PAR(2) to expose a tethered ligand that binds to the cleaved receptor. Despite this irreversible activation, PAR(2) signalling is attenuated by beta-arrestin-mediated desensitization and endocytosis, and by lysosomal targeting and degradation, which requires ubiquitination of PAR(2). beta-Arrestins also act as scaffolds for the assembly of multi-protein signalling complexes that determine the location and function of activated mitogen-activated protein kinases. Observations of PAR(2)-deficient mice support a role for PAR(2) in inflammation, and many of the effects of PAR(2) activators promote inflammation. Inflammation is mediated in part by activation of PAR(2) in the peripheral nervous system, which results in neurogenic inflammation and hyperalgesia.

The GCM–Reality Intercomparison Project for SPARC (GRIPS): scientific issues and initial results

To investigate the effects of the middle atmosphere on climate, the World Climate Research Programme is supporting the project "Stratospheric Processes and their Role in Climate" (SPARC). A central theme of SPARC, to examine model simulations of the coupled troposphere—middle atmosphere system, is being performed through the initiative called GRIPS (GCM—Reality Intercomparison Project for SPARC). In this paper, an overview of the objectives of GRIPS is given. Initial activities include an assessment of the performance of middle atmosphere climate models, and preliminary results from this evaluation are presented here. It is shown that although all 13 models evaluated represent most major features of the mean atmospheric state, there are deficiencies in the magnitude and location of the features, which cannot easily be traced to the formulation (resolution or the parameterizations included) of the models. Most models show a cold bias in all locations, apart from the tropical tropopause region where they can be either too warm or too cold. The strengths and locations of the major jets are often misrepresented in the models. Looking at three—dimensional fields reveals, for some models, more severe deficiencies in the magnitude and positioning of the dominant structures (such as the Aleutian high in the stratosphere), although undersampling might explain some of these differences from observations. All the models have shortcomings in their simulations of the present—day climate, which might limit the accuracy of predictions of the climate response to ozone change and other anomalous forcing.

Bridging the segmentation theory/practice divide

More than thirty years ago, Wind's seminal review of research in market segmentation culminated with a research agenda for the subject area. In the intervening period, research has focused on the development of segmentation bases and models, segmentation research techniques and the identification of statistically sound solutions. Practical questions about implementation and the integration of segmentation into marketing strategy have received less attention, even though practitioners are known to struggle with the actual practice of segmentation. This special issue is motivated by this tension between theory and practice, which has shaped and continues to influence the research priorities for the field. Although many years may have elapsed since Wind's original research agenda, pressing questions about effectiveness and productivity apparently remain; namely: (i) concerns about the link between segmentation and performance, and its measurement; and (ii) the notion that productivity improvements arising from segmentation are only achievable if the segmentation process is effectively implemented. There were central themes to the call for papers for this special issue, which aims to develop our understanding of segmentation value, productivity and strategies, and managerial issues and implementation.

Implementation rules to bridge the theory/practice divide in market segmentation

Despite an extensive market segmentation literature, applied academic studies which bridge segmentation theory and practice remain a priority for researchers. The need for studies which examine the segmentation implementation barriers faced by organisations is particularly acute. We explore segmentation implementation through the eyes of a European utilities business, by following its progress through a major segmentation project. The study reveals the character and impact of implementation barriers occurring at different stages in the segmentation process. By classifying the barriers, we develop implementation "rules" for practitioners which are designed to minimise their occurrence and impact. We further contribute to the literature by developing a deeper understanding of the mechanisms through which these implementation rules can be applied.

Evaluation of positioning error-induced pixel shifts on satellite linear push-broom imagery

Georeferencing is one of the major tasks of satellite-borne remote sensing. Compared to traditional indirect methods, direct georeferencing through a Global Positioning System/inertial navigation system requires fewer and simpler steps to obtain exterior orientation parameters of remotely sensed images. However, the pixel shift caused by geographic positioning error, which is generally derived from boresight angle as well as terrain topography variation, can have a great impact on the precision of georeferencing. The distribution of pixel shifts introduced by the positioning error on a satellite linear push-broom image is quantitatively analyzed. We use the variation of the object space coordinate to simulate different kinds of positioning errors and terrain topography. Then a total differential method was applied to establish a rigorous sensor model in order to mathematically obtain the relationship between pixel shift and positioning error. Finally, two simulation experiments are conducted using the imaging parameters of Chang’ E-1 satellite to evaluate two different kinds of positioning errors. The experimental results have shown that with the experimental parameters, the maximum pixel shift could reach 1.74 pixels. The proposed approach can be extended to a generic application for imaging error modeling in remote sensing with terrain variation.

Customer service 140 characters at a time: the users’ perspective

Electronic word of mouth (eWoM) has been adopted by Internet users as a way of communicating their consumption preferences and experiences. Consumers are able to reach out to others, unknown to them, and have online conversations that can influence their behaviour. Organisations need to understand how to respond to these brand-related conversations conducted via social media. By looking through the lens of social capital, this paper contributes to social media and social capital research by studying the perceptions that 44 social media users have of companies that interact with them online. The users value social networks and support as part of their online relationships. However, several new value categories are identified when compared to previous research. Further research is required to investigate possible segmentation approaches and alternative methodological choices.

Finding vikings in the Danelaw

Historical, artefactual and place-name evidence indicates that Scandinavian migrants moved to eastern England in the ninth century AD, settling in the Danelaw. However, only a handful of characteristically Scandinavian burials have been found in the region. One, widely held, explanation is that most of these Scandinavian settlers quickly adopted local Christian burial customs, thus leaving Scandinavians indistinguishable from the Anglo-Saxon population. We undertook osteological and isotopic analysis to investigate the presence of first-generation Scandinavian migrants. Burials from Masham were typical of the later Anglo-Saxon period and included men, women and children. The location and positioning of the four adult burials from Coppergate, however, are unusual for Anglo-Scandinavian York. None of the skeletons revealed interpersonal violence. Isotopic evidence did not suggest a marine component in the diet of either group, but revealed migration on a regional, and possibly an international, scale. Combined strontium and oxygen isotope analysis should be used to investigate further both regional and Scandinavian migration in the later Anglo-Saxon period.

Transcription factor NF-kappaB is transported to the nucleus via cytoplasmic dynein/dynactin motor complex in hippocampal neurons

Background Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-κB. Transcription factors of the NF-κB family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. Principal Findings In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-κB to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-κB p65 and reduces NF-κB-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-κB p65 is essential for this binding. Conclusion This study shows the molecular mechanism for the retrograde transport of activated NF-κB from distant synaptic sites towards the nucleus.

Identification of novel cholesteatoma-related gene expression signatures using full-genome microarrays

This study demonstrates that the expression profile of cholesteatoma is similar to a metastatic tumour and chronically inflamed tissue. Based on the investigated profiles we present novel protein-protein interaction and signal transduction networks, which include cholesteatoma-regulated transcripts and may be of great value for drug targeting and therapy development.