Earnings distribution, corporate governance and CEO pay

We investigate the relationship between earnings differentials and the pay of CEOs of 190 British companies between 1970 and 1990. We find that (i) changes in the differential between the 90th and 50th weekly earnings percentiles for non-manual adult male workers [90:50] explain changes in the level of real CEO salary and bonus in our sample of companies; (ii) changes in this differential also account for changes in the elasticity of CEO pay to firm size; (iii) a broader measure of earnings inequality does far worse than 90:50 at explaining changes in both the level and the firm size elasticity of CEO pay; (iv) fitting the model on data for 1970-1983 and predicting pay levels for the period starting with the widespread adoption of executive share option schemes in 1984, we find a structural break in the relationship between lower management pay differentials and the pay of the CEO. We conclude first that top executive pay prior to 1984 was a stable function of both firm size and earnings differentials lower on the administrative ladder, consistent with a hypothesis advanced by Herbert Simon in 1957; and second that the use of share options from 1984 onward represents not simply a change in the mode of top executive compensation, but a de -linking of the pay of top executives and that of their subordinates

Geroch--Kinnersley--Chitre group for Dilaton--Axion Gravity

Kinnersley--type representation is constructed for the four--dimensional Einstein--Maxwell--dilaton--axion system restricted to space--times possessing two non--null commuting Killing symmetries. New representation essentially uses the matrix--valued $SL(2,R)$ formulation and effectively reduces the construction of the Geroch group to the corresponding problem for the vacuum Einstein equations. An infinite hierarchy of potentials is introduced in terms of $2\times 2$ real symmetric matrices generalizing the scalar hierarchy of Kinnersley--Chitre known for the vacuum Einstein equations.Comment: Published in ``Quantum Field Theory under the Influence of External Conditions'', M. Bordag (Ed.) (Proc. of the International Workshop, Leipzig, Germany, 18--22 September 1995), B.G. Teubner Verlagsgessellschaft, Stuttgart--Leipzig, 1996, pp. 228-23

Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans

This is the final version of the article. Available from the publisher via the DOI in this record.Dysregulation of splicing factor expression and altered alternative splicing are associated with aging in humans and other species, and also with replicative senescence in cultured cells. Here, we assess whether expression changes of key splicing regulator genes and consequent effects on alternative splicing are also associated with strain longevity in old and young mice, across 6 different mouse strains with varying lifespan (A/J, NOD.B10Sn-H2(b) /J, PWD.Phj, 129S1/SvlmJ, C57BL/6J and WSB/EiJ). Splicing factor expression and changes to alternative splicing were associated with strain lifespan in spleen and to a lesser extent in muscle. These changes mainly involved hnRNP splicing inhibitor transcripts with most changes more marked in spleens of young animals from long-lived strains. Changes in spleen isoform expression were suggestive of reduced cellular senescence and retained cellular proliferative capacity in long-lived strains. Changes in muscle isoform expression were consistent with reduced pro-inflammatory signalling in longer-lived strains. Two splicing regulators, HNRNPA1 and HNRNPA2B1, were also associated with parental longevity in humans, in the InCHIANTI aging study. Splicing factors may represent a driver, mediator or early marker of lifespan in mouse, as expression differences were present in the young animals of long-lived strains. Changes to alternative splicing patterns of key senescence genes in spleen and key remodelling genes in muscle suggest that correct regulation of alternative splicing may enhance lifespan in mice. Expression of some splicing factors in humans was also associated with parental longevity, suggesting that splicing regulation may also influence lifespan in humans.The authors would like to acknowledge the Wellcome Trust (grant number WT097835MF LWH, DM), and NIH-NIA grant number AG038070 to The Jackson Laboratory for providing the funding for this study

Environmental conditions during breeding modify the strength of mass-dependent carry-over effects in a migratory bird

This is the final version of the article. Available from the publisher via the DOI in this record.In many animals, processes occurring in one season carry over to influence reproductive success and survival in future seasons. The strength of such carry-over effects is unlikely to be uniform across years, yet our understanding of the processes that are capable of modifying their strength remains limited. Here we show that female light-bellied Brent geese with higher body mass prior to spring migration successfully reared more offspring during breeding, but only in years where environmental conditions during breeding were favourable. In years of bad weather during breeding, all birds suffered reduced reproductive output irrespective of pre-migration mass. Our results suggest that the magnitude of reproductive benefits gained by maximising body stores to fuel breeding fluctuates markedly among years in concert with conditions during the breeding season, as does the degree to which carry-over effects are capable of driving variance in reproductive success among individuals. Therefore while carry-over effects have considerable power to drive fitness asymmetries among individuals, our ability to interpret these effects in terms of their implications for population dynamics is dependent on knowledge of fitness determinants occurring in subsequent seasons. XAH was funded by NERC grant (NE⁄F008058⁄1) with a Wildfowl & Wetlands Trust CASE partnership and RI by NERC grant (NE⁄F021690⁄1), both awarded to SB. SB is funded by an ERC Consolidator's Grant: STATEMIG 310820. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice

This is the final version of the article. Available from Springer Nature via the DOI in this record.MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3' untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR. Expression levels of 3 microRNAs were robustly associated with strain lifespan, after correction for multiple statistical testing (miR-203-3p [β-coefficient = -0.6447, p = 4.8 × 10(-11)], miR-664-3p [β-coefficient = 0.5552, p = 5.1 × 10(-8)] and miR-708-5p [β-coefficient = 0.4986, p = 1.6 × 10(-6)]). Pathway analysis of binding sites for these three microRNAs revealed enrichment of target genes involved in key aging and longevity pathways including mTOR, FOXO and MAPK, most of which also demonstrated associations with longevity. Our results suggests that miR-203-3p, miR-664-3p and miR-708-5p may be implicated in pathways determining lifespan in mammals.This work was funded by the Wellcome Trust (grant number WT097835MF to D. Melzer and L.W. Harries), and the NIH-NIA (grant number AG038070 to The Jackson Laboratory)

Why Some Interfaces Cannot be Sharp

A central goal of modern materials physics and nanoscience is control of materials and their interfaces to atomic dimensions. For interfaces between polar and non-polar layers, this goal is thwarted by a polar catastrophe that forces an interfacial reconstruction. In traditional semiconductors this reconstruction is achieved by an atomic disordering and stoichiometry change at the interface, but in multivalent oxides a new option is available: if the electrons can move, the atoms don`t have to. Using atomic-scale electron energy loss spectroscopy we find that there is a fundamental asymmetry between ionically and electronically compensated interfaces, both in interfacial sharpness and carrier density. This suggests a general strategy to design sharp interfaces, remove interfacial screening charges, control the band offset, and hence dramatically improving the performance of oxide devices.Comment: 12 pages of text, 6 figure

The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses

A Revised Design for Microarray Experiments to Account for Experimental Noise and Uncertainty of Probe Response

Background Although microarrays are analysis tools in biomedical research, they are known to yield noisy output that usually requires experimental confirmation. To tackle this problem, many studies have developed rules for optimizing probe design and devised complex statistical tools to analyze the output. However, less emphasis has been placed on systematically identifying the noise component as part of the experimental procedure. One source of noise is the variance in probe binding, which can be assessed by replicating array probes. The second source is poor probe performance, which can be assessed by calibrating the array based on a dilution series of target molecules. Using model experiments for copy number variation and gene expression measurements, we investigate here a revised design for microarray experiments that addresses both of these sources of variance. Results Two custom arrays were used to evaluate the revised design: one based on 25 mer probes from an Affymetrix design and the other based on 60 mer probes from an Agilent design. To assess experimental variance in probe binding, all probes were replicated ten times. To assess probe performance, the probes were calibrated using a dilution series of target molecules and the signal response was fitted to an adsorption model. We found that significant variance of the signal could be controlled by averaging across probes and removing probes that are nonresponsive or poorly responsive in the calibration experiment. Taking this into account, one can obtain a more reliable signal with the added option of obtaining absolute rather than relative measurements. Conclusion The assessment of technical variance within the experiments, combined with the calibration of probes allows to remove poorly responding probes and yields more reliable signals for the remaining ones. Once an array is properly calibrated, absolute quantification of signals becomes straight forward, alleviating the need for normalization and reference hybridizations

Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts