Laplacian eigenvalues functionals and metric deformations on compact manifolds

In this paper, we investigate critical points of the Laplacian's eigenvalues considered as functionals on the space of Riemmannian metrics or a conformal class of metrics on a compact manifold. We obtain necessary and sufficient conditions for a metric to be a critical point of such a functional. We derive specific consequences concerning possible locally maximizing metrics. We also characterize critical metrics of the ratio of two consecutive eigenvalues

In vivo cannabidiol treatment improves endothelium-dependent vasorelaxation in mesenteric arteries of Zucker diabetic fatty rats

Background and purpose: We have shown that in vitro treatment with cannabidiol (CBD, 2 h) enhances endothelial function in arteries from Zucker diabetic fatty (ZDF) rats, partly due to a cyclooxygenase (COX)-mediated mechanism. The aim of the present study was to determine whether treatment with CBD in vivo would also enhance endothelial function. Experimental approach: Male ZDF rats, or ZDF Lean rats, were treated for 7 days (daily i.p. injection) with either 10mg/kg CBD or vehicle (n D 6 per group). Sections of mesenteric resistance arteries, femoral arteries and thoracic aortae were mounted on a wire myograph, and cumulative concentration-response curves to endothelium-dependent (acetylcholine, ACh, 1 nM–100 mM) or endothelium-independent (sodium nitroprusside, SNP, 1 nM–100 mM) agents were constructed. Multiplex analysis was used to measure serum metabolic and cardiovascular biomarkers. Key results: Vasorelaxation to ACh was significantly enhanced in mesenteric arteries from CBD-treated ZDF rats, but not ZDF Lean rats. The enhanced vasorelaxation in ZDF mesenteric arteries was no longer observed after COX inhibition using indomethacin or nitric oxide (NO) inhibition using L-NAME. Increased levels of serum c-peptide, insulin and intracellular adhesion molecule-1 observed in the ZDF compared to ZDF Lean rats were no longer significant after 7 days CBD treatment. Conclusion and implications: Short-term in vivo treatment with CBD improves ex vivo endothelium-dependent vasorelaxation in mesenteric arteries from ZDF rats due to COX- or NO-mediated mechanisms, and leads to improvements in serum biomarkers

Chemically specifi C multiscale modeling of clay-polymer nanocomposites reveals intercalation dynamics, tactoid self-assembly and emergent materials properties

A quantitative description is presented of the dynamical process of polymer intercalation into clay tactoids and the ensuing aggregation of polymerentangled tactoids into larger structures, obtaining various characteristics of these nanocomposites, including clay-layer spacings, out-of-plane clay-sheet bending energies, X-ray diffractograms, and materials properties. This model of clay-polymer interactions is based on a three-level approach, which uses quantum mechanical and atomistic descriptions to derive a coarse-grained yet chemically specifi c representation that can resolve processes on hitherto inaccessible length and time scales. The approach is applied to study collections of clay mineral tactoids interacting with two synthetic polymers, poly(ethylene glycol) and poly(vinyl alcohol). The controlled behavior of layered materials in a polymer matrix is centrally important for many engineering and manufacturing applications. This approach opens up a route to computing the properties of complex soft materials based on knowledge of their chemical composition, molecular structure, and processing conditions.This work was funded in part by the EU FP7 MAPPER project (grant number RI-261507) and the Qatar National Research Fund (grant number 09–260–1–048). Supercomputing time was provided by PRACE on JUGENE (project PRA044), the Hartree Centre (Daresbury Laboratory) on BlueJoule and BlueWonder via the CGCLAY project, and on HECToR and ARCHER, the UK national supercomputing facility at the University of Edinburgh, via EPSRC through grants EP/F00521/1, EP/E045111/1, EP/I017763/1 and the UK Consortium on Mesoscopic Engineering Sciences (EP/L00030X/1). The authors are grateful to Professor Julian Evans for stimulating discussions during the course of this project. Data-storage and management services were provided by EUDAT (grant number 283304)

Regulation of expression of the rat orthologue of mouse double minute 2 (MDM2) by H2O2-induced oxidative stress in neonatal rat cardiac myocytes.

The Mdm2 ubiquitin ligase is an important regulator of p53 abundance and p53-dependent apoptosis. Mdm2 expression is frequently regulated by a p53 Mdm2 autoregulatory loop whereby p53 stimulates Mdm2 expression and hence its own degradation. Although extensively studied in cell lines, relatively little is known about Mdm2 expression in heart where oxidative stress (exacerbated during ischemia-reperfusion) is an important pro-apoptotic stimulus. We demonstrate that Mdm2 transcript and protein expression are induced by oxidative stress (0.2 mm H(2)O(2)) in neonatal rat cardiac myocytes. In other cells, constitutive Mdm2 expression is regulated by the P1 promoter (5' to exon 1), with inducible expression regulated by the P2 promoter (in intron 1). In myocytes, H(2)O(2) increased Mdm2 expression from the P2 promoter, which contains two p53-response elements (REs), one AP-1 RE, and two Ets REs. H(2)O(2) did not detectably increase expression of p53 mRNA or protein but did increase expression of several AP-1 transcription factors. H(2)O(2) increased binding of AP-1 proteins (c-Jun, JunB, JunD, c-Fos, FosB, and Fra-1) to an Mdm2 AP-1 oligodeoxynucleotide probe, and chromatin immunoprecipitation assays showed it increased binding of c-Jun or JunB to the P2 AP-1 RE. Finally, antisense oligonucleotide-mediated reduction of H(2)O(2)-induced Mdm2 expression increased caspase 3 activation. Thus, increased Mdm2 expression is associated with transactivation at the P2 AP-1 RE (rather than the p53 or Ets REs), and Mdm2 induction potentially represents a cardioprotective response to oxidative stress

The treatment experiences of people living with ileostomies: an interpretative phenomenological analysis

AIMS: To explore treatment and healthcare experiences of people living with ileostomies, so nurses can build on best practice whilst caring for these patients. Background Ileostomies, in which the small intestine is re-directed out of a stoma in the abdominal wall so waste is collected using a bag, are used to treat conditions including Inflammatory Bowel Disease. Existing research suggests that although life with a stoma can be challenging, ileostomy patients are largely supported by multi-disciplinary teams. However, more research is needed to understand the nuances of these relationships and experiences of treatment, with a view to improving clinical care. DESIGN: Participants took part in semi-structured interviews consisting of open ended questions about their experiences of life with an ileostomy and their treatments and time in hospital. Points of interest were followed up. Data were collected between July and December of 2014. METHODS: The qualitative method Interpretative Phenomenological Analysis was used to analyse interviews with 21 people living with ileostomies. FINDINGS: We present findings from two clinical themes: Issues around treatment and Relationships with multi-disciplinary teams. Surgical complications were common, and several participants reported concerns about addiction to painkillers. Varying attitudes were found around reversal surgery. Many reported experiencing distressing, dehumanising care, whilst some felt supported by excellent healthcare providers. CONCLUSION: People living with ileostomies have a very mixed experience of multi-disciplinary teams and treatments, and much could be done to support them more fully. For example, more information about ileostomies could be given to patients and more training given to nurses around stomas

The histone chaperones Vps75 and Nap1 form ring-like, tetrameric structures in solution

NAP-1 fold histone chaperones play an important role in escorting histones to and from sites of nucleosome assembly and disassembly. The two NAP-1 fold histone chaperones in budding yeast, Vps75 and Nap1, have previously been crystalized in a characteristic homodimeric conformation. In this study, a combination of small angle X-ray scattering, multi angle light scattering and pulsed electron–electron double resonance approaches were used to show that both Vps75 and Nap1 adopt ring-shaped tetrameric conformations in solution. This suggests that the formation of homotetramers is a common feature of NAP-1 fold histone chaperones. The tetramerisation of NAP-1 fold histone chaperones may act to shield acidic surfaces in the absence of histone cargo thus providing a ‘self-chaperoning’ type mechanism

On the universality of density profiles

We use the secondary infall model described in Del Popolo (2009), which takes into account the effect of dynamical friction, ordered and random angular momentum, baryons adiabatic contraction and dark matter baryons interplay, to study how in- ner slopes of relaxed LCDM dark matter (DM) halos with and without baryons (baryons+DM, and pure DM) depend on redshift and on halo mass. We apply the quoted method to structures on galactic scales and clusters of galaxies scales. We find that the inner logarithmic density slope, of dark matter halos with baryons has a significant dependence on halo mass and redshift with slopes ranging from 0 for dwarf galaxies to 0.4 for objects of M = 10^13M_solar and 0.94 for M = 10^15M_solar clusters of galaxies. Structures slopes increase with increasing redshift and this trend reduces going from galaxies to clusters. In the case of density profiles constituted just of dark matter the mass and redshift dependence of slope is very slight. In this last case, we used the Merrit et al. (2006) analysis who compared N-body density profiles with various parametric models finding systematic variation in profile shape with halo mass. This last analysis suggests that the galaxy-sized halos obtained with our model have a different shape parameter, i.e. a different mass distribution, than the cluster-sized halos, obtained with the same model. The results of the present paper argue against universality of density profiles constituted by dark matter and baryons and confirm claims of a systematic variation in profile shape with halo mass, for dark matter halos.Comment: 11 pages, 5 figure

Polyubiquitin binding to ABIN1 is required to prevent autoimmunity

The protein ABIN1 possesses a polyubiquitin-binding domain homologous to that present in nuclear factor kappa B (NF-kappa B) essential modulator (NEMO), a component of the inhibitor of NF-kappa B (I kappa B) kinase (IKK) complex. To address the physiological significance of polyubiquitin binding, we generated knockin mice expressing the ABIN1[D485N] mutant instead of the wild-type (WT) protein. These mice developed all the hallmarks of autoimmunity, including spontaneous formation of germinal centers, isotype switching, and production of autoreactive antibodies. Autoimmunity was suppressed by crossing to MyD88(-/-) mice, demonstrating that toll-like receptor (TLR)-MyD88 signaling pathways are needed for the phenotype to develop. The B cells and myeloid cells of the ABIN1[D485N] mice showed enhanced activation of the protein kinases TAK, IKK-alpha/beta, c-Jun N-terminal kinases, and p38 alpha mitogen-activated protein kinase and produced more IL-6 and IL-12 than WT. The mutant B cells also proliferated more rapidly in response to TLR ligands. Our results indicate that the interaction of ABIN1 with polyubiquitin is required to limit the activation of TLR-MyD88 pathways and prevent autoimmunity

Equilibrium configurations of two charged masses in General Relativity

An asymptotically flat static solution of Einstein-Maxwell equations which describes the field of two non-extreme Reissner - Nordstr\"om sources in equilibrium is presented. It is expressed in terms of physical parameters of the sources (their masses, charges and separating distance). Very simple analytical forms were found for the solution as well as for the equilibrium condition which guarantees the absence of any struts on the symmetry axis. This condition shows that the equilibrium is not possible for two black holes or for two naked singularities. However, in the case when one of the sources is a black hole and another one is a naked singularity, the equilibrium is possible at some distance separating the sources. It is interesting that for appropriately chosen parameters even a Schwarzschild black hole together with a naked singularity can be "suspended" freely in the superposition of their fields.Comment: 4 pages; accepted for publication in Phys. Rev.