Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.

Chromosome segregation begins when the cysteine protease, separase, cleaves the Scc1 subunit of cohesin at the metaphase-to-anaphase transition. Separase is inhibited prior to metaphase by the tightly bound securin protein, which contains a pseudosubstrate motif that blocks the separase active site. To investigate separase substrate specificity and regulation, here we develop a system for producing recombinant, securin-free human separase. Using this enzyme, we identify an LPE motif on the Scc1 substrate that is distinct from the cleavage site and is required for rapid and specific substrate cleavage. Securin also contains a conserved LPE motif, and we provide evidence that this sequence blocks separase engagement of the Scc1 LPE motif. Our results suggest that rapid cohesin cleavage by separase requires a substrate docking interaction outside the active site. This interaction is blocked by securin, providing a second mechanism by which securin inhibits cohesin cleavage

CEO pay, shareholder returns, and accounting profits

We assess the impact on CEO pay (including salary, cash bonus, and benefits in kind) of changes in both accounting and shareholder returns in 99 British companies in the years 1972-89. After correcting for heterogeneity biases inherent in the standard specifications of the problem, we find a strong positive relationship between CEO pay and within-company changes in shareholder returns, and no statistically significant relationship between CEO pay and within-company changes in accounting returns. Differences between firms in long-term average profitability do appear to have a substantial effect on CEO pay, while differences between firms in shareholder returns add nothing to the within-firm pay dynamics.These findings call into question the rationale for explicitly share-based incentive schemes

Conserved Charges in Einstein Gauss-Bonnet theory

Using Noether's identities, we define a superpotential with respect to a background for the Einstein Gauss-Bonnet theory of gravity. As an example, we show that its associated conserved charge yields the mass-energy of a D-dimensional Gauss-Bonnet black hole in an anti-de Sitter spacetime.Comment: 17 pages, LaTeX, references added, typos corrected, version to appear in Class. Quant. Gra

Wesson's IMT with a Weylian bulk

The foundations of Wesson's induced matter theory are analyzed. It is shown that the 5D empty bulk must be regarded rather as a Weylian space than as a Riemannian one.The framework of a Weyl-Dirac version of Wesson's theory is elaborated and discussed. The bulk possesses in addition to the metric tensor a Weylian connection vector as well Dirac's gauge function; there are no sources (mass, current) in the bulk. On the 4D brane one obtains a geometrically based unified theory of gravitation and electromagnetism with mass, currents and equations induced by the 5D bulkComment: 29 page

Large-density field theory, viscosity, and "2kF2k_F" singularities from string duals

We analyze systems where an effective large-N expansion arises naturally in gauge theories without a large number of colors: a sufficiently large charge density alone can produce a perturbative string ('tHooft) expansion. One example is simply the well-known NS5/F1 system dual to $AdS_3\times T^4\times S^3$, here viewed as a 5+1 dimensional theory at finite density. This model is completely stable, and we find that the existing string-theoretic solution of this model yields two interesting results. First, it indicates that the shear viscosity is not corrected by $\alpha'$ effects in this system. For flow perpendicular to the F1 strings the viscosity to entropy ratio take the usual value $1/4\pi$, but for flow parallel to the F1's it vanishes as $T^2$ at low temperature. Secondly, it encodes singularities in correlation functions coming from low-frequency modes at a finite value of the momentum along the $T^4$ directions. This may provide a strong coupling analogue of finite density condensed matter systems for which fermionic constituents of larger operators contribute so-called "$2k_F$" singularities. In the NS5/F1 example, stretched strings on the gravity side play the role of these composite operators. We explore the analogue for our system of the Luttinger relation between charge density and the volume bounded by these singular surfaces. This model provides a clean example where the string-theoretic UV completion of the gravity dual to a finite density field theory plays a significant and calculable role.Comment: 28 pages. v2: added reference

Relativistic conservation laws and integral constraints for large cosmological perturbations

For every mapping of a perturbed spacetime onto a background and with any vector field $\xi$ we construct a conserved covariant vector density $I(\xi)$, which is the divergence of a covariant antisymmetric tensor density, a "superpotential". $I(\xi)$ is linear in the energy-momentum tensor perturbations of matter, which may be large; $I(\xi)$ does not contain the second order derivatives of the perturbed metric. The superpotential is identically zero when perturbations are absent. By integrating conserved vectors over a part \Si of a hypersurface $S$ of the background, which spans a two-surface \di\Si, we obtain integral relations between, on the one hand, initial data of the perturbed metric components and the energy-momentum perturbations on \Si and, on the other hand, the boundary values on \di\Si. We show that there are as many such integral relations as there are different mappings, $\xi$'s, \Si's and \di\Si's. For given boundary values on \di\Si, the integral relations may be interpreted as integral constraints (e.g., those of Traschen) on local initial data including the energy-momentum perturbations. Conservation laws expressed in terms of Killing fields \Bar\xi of the background become "physical" conservation laws. In cosmology, to each mapping of the time axis of a Robertson-Walker space on a de Sitter space with the same spatial topology there correspond ten conservation laws. The conformal mapping leads to a straightforward generalization of conservation laws in flat spacetimes. Other mappings are also considered. ...Comment: This paper, published 7 years ago, was found useful by some researchers but originally was not put on the gr-qc website. Now it has been retyped with very minor changes: few wordings have been modified and several misprints occurring in the printed version correcte

An exploration of factors affecting the long term psychological impact and deterioration of mental health in flooded households

The long term psychological effect of the distress and trauma caused by the memory of damage and losses associated with flooding of communities remains an under researched impact of flooding. This is particularly important for communities that are likely to be repeatedly flooded where levels of mental health disorder will damage long term resilience to future flooding.There are a variety of factors that affect the prevalence of mental health disorders in the aftermath of flooding including pre-existing mental health, socio-economic factors and flood severity. However previous research has tended to focus on the short term impacts immediately following the flood event and much less focus has been given to the longer terms effects of flooding. Understanding of factors affecting the longer term mental health outcomes for flooded households is critical in order to support communities in improving social resilience. Hence, the aim of this study was to explore the characteristics associated with psychological distress and mental health deterioration over the longer term.The research examined responses from a postal survey of households flooded during the 2007 flood event across England. Descriptive statistics, correlation analysis and binomial logistic regression were applied to data representing household characteristics, flood event characteristics and post-flood stressors and coping strategies. These factors were related to reported measures of stress, anxiety, depression and mental health deterioration. The results showed that household income, depth of flooding; having to move out during reinstatement and mitigating actions are related to the prevalence of psycho-social symptoms in previously flooded households. In particular relocation and household income were the most predictive factors. The practical implication of these findings for recovery after flooding are: to consider the preferences of households in terms of the need to move out during restorative building works and the financial resource constraints that may lead to severe mental hardship. In addition the findings suggest that support with installing mitigation measures may lead to improved mental health outcomes for communities at risk

On Global Conservation Laws at Null Infinity

The ``standard'' expressions for total energy, linear momentum and also angular momentum of asymptotically flat Bondi metrics at null infinity are also obtained from differential conservation laws on asymptotically flat backgrounds, derived from a quadratic Lagrangian density by methods currently used in classical field theory. It is thus a matter of taste and commodity to use or not to use a reference spacetime in defining these globally conserved quantities. Backgrounds lead to N\oe ther conserved currents; the use of backgrounds is in line with classical views on conservation laws. Moreover, the conserved quantities are in principle explicitly related to the sources of gravity through Einstein's equations, while standard definitions are not. The relations depend, however, on a rule for mapping spacetimes on backgrounds

The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

Impact of Genetic Variation in SORCS1 on Memory Retention

We previously reported that genetic variants in SORCS1 increase the risk of AD, that over-expression of SorCS1 reduces γ-secretase activity and Aβ levels, and that SorCS1 suppression increases γ-secretase processing of APP and Aβ levels. We now explored the effect of variation in SORCS1 on memory.We explored associations between SORCS1-SNPs and memory retention in the NIA-LOAD case control dataset (162 cases,670 controls) and a cohort of Caribbean Hispanics (549 cases,544 controls) using single marker and haplotype analyses.Three SNPs in intron 1, were associated with memory retention in the NIA-LOAD dataset or the Caribbean Hispanic dataset (rs10884402(A allele:β = -0.15,p = 0.008), rs7078098(C allele:β = 0.18,p = 0.007) and rs950809(C allele:β = 0.17,p = 0.008)) and all three SNPs were significant in a meta-analysis of both datasets (0.002<p<0.03). The corresponding A-T-T haplotype for these SNPs was associated with lower scores in both datasets (p = 0.02,p = 0.0009), and the complementary G-C-C haplotype was associated with higher scores in NIA-LOAD (p = 0.02). These associations were restricted to cases.Variation in intron 1 in SORCS1 is associated with memory changes in AD