Physical activity for cancer survivors: meta-analysis of randomised controlled trials

Objective To systematically evaluate the effects of physical activity in adult patients after completion of main treatment related to cancer

Bond operator theory of doped antiferromagnets: from Mott insulators with bond-centered charge order, to superconductors with nodal fermions

The ground states and excitations of two-dimensional insulating and doped Mott insulators are described by a bond operator formalism. While the method represents the degrees of freedom of an arbitrary antiferromagnet exactly, it is especially suited to systems in which there is a natural pairing of sites into bonds, as in states with spontaneous or explicit spin-Peierls order (or bond-centered charge order). In the undoped insulator, as discussed previously, we obtain both paramagnetic and magnetically-ordered states. We describe the evolution of superconducting order in the ground state with increasing doping--at low doping, the superconductivity is weak, can co-exist with magnetic order, and there are no gapless spin 1/2 fermionic excitations; at high doping, the magnetic order is absent and we obtain a BCS d-wave superconductor with gapless spin 1/2, nodal fermions. We present the critical theory describing the onset of these nodal fermionic excitations. We discuss the evolution of the spin spectrum, and obtain regimes where a spin 1 exciton contributes a sharp resonance in the dynamic spin susceptiblity. We also discuss the experimental consequences of low-energy, dynamically fluctuating, spin-Peierls order in an isotropic CuO_2 plane--we compute consequences for the damping and dispersion of an optical phonon involving primarily the O ions, and compare the results with recent neutron scattering measurements of phonon spectra.Comment: 16 pages + 14 pages of appendices, 18 figures; (v3) expanded discussion of theory and experimental implications; (v4) Removed some introductory review discussion and moved it to cond-mat/010823

The Angio-Fibrotic Switch of VEGF and CTGF in Proliferative Diabetic Retinopathy

BACKGROUND: In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) cause blindness by neovascularization and subsequent fibrosis, but their relative contribution to both processes is unknown. We hypothesize that the balance between levels of pro-angiogenic VEGF and pro-fibrotic CTGF regulates angiogenesis, the angio-fibrotic switch, and the resulting fibrosis and scarring. METHODS/PRINCIPAL FINDINGS: VEGF and CTGF were measured by ELISA in 68 vitreous samples of patients with proliferative DR (PDR, N = 32), macular hole (N = 13) or macular pucker (N = 23) and were related to clinical data, including degree of intra-ocular neovascularization and fibrosis. In addition, clinical cases of PDR (n = 4) were studied before and after pan-retinal photocoagulation and intra-vitreal injections with bevacizumab, an antibody against VEGF. Neovascularization and fibrosis in various degrees occurred almost exclusively in PDR patients. In PDR patients, vitreous CTGF levels were significantly associated with degree of fibrosis and with VEGF levels, but not with neovascularization, whereas VEGF levels were associated only with neovascularization. The ratio of CTGF and VEGF was the strongest predictor of degree of fibrosis. As predicted by these findings, patients with PDR demonstrated a temporary increase in intra-ocular fibrosis after anti-VEGF treatment or laser treatment. CONCLUSIONS/SIGNIFICANCE: CTGF is primarily a pro-fibrotic factor in the eye, and a shift in the balance between CTGF and VEGF is associated with the switch from angiogenesis to fibrosis in proliferative retinopathy

Framing the Paralympic Games: A Mixed-Methods Analysis of Spanish Media Coverage of the Beijing 2008 and London 2012 Paralympic Games

In recent years, there has been an increased emergence of studies focusing on the media coverage of the Paralympic Games. Until recently, studies have predominately used quantitative content analyses that, although providing useful interrogation of observational patterns, limits the understanding of and appreciation for the contexts that may have shaped the production of information. By focusing exclusively on the ‘what’ and on the ‘how much’ it is difficult to reveal the ‘why’ and to identify the underlying motives of any changes. This paper recognizes the nuances of the editorial decision-making process by using a mixed methods approach; employing quantitative and qualitative data drawn from a case study focusing on the Spanish media coverage of the 2008 and 2012 Paralympic Games. An initial content analysis of all news published in Spain’s twelve highest-circulation newspapers during Beijing 2008 and London 2012 Paralympic Games was undertaken. Subsequently, 15 semi-structured interviews were conducted with journalists that were also sent to these two iterations of the Paralympic Games by Spanish media. Drawing on conceptualisations of media framing, the results highlight that the numerical data alone shed insufficient light on the complexity of the news-making process. The semi-structured interviews brought to light issues such as editorial management buoyed by commercial imperatives, and organisational interjection in journalists’ narratives and authorship, that also contoured coverage and content. In addition to further debate about the complexities of media coverage of Paralympic sport, the study also underscores the utility of incorporating and combining qualitative and quantitative methodologies within sport media and communication research

3T3 Cell Lines Stably Expressing Pax6 or Pax6(5a) – A New Tool Used for Identification of Common and Isoform Specific Target Genes

Pax6 and Pax6(5a) are two isoforms of the evolutionary conserved Pax6 gene often co-expressed in specific stochiometric relationship in the brain and the eye during development. The Pax6(5a) protein differs from Pax6 by having a 14 amino acid insert in the paired domain, causing the two proteins to have different DNA binding specificities. Difference in functions during development is proven by the fact that mutations in the 14 amino acid insertion for Pax6(5a) give a slightly different eye phenotype than the one described for Pax6. Whereas quite many Pax6 target genes have been published during the last years, few Pax6(5a) specific target genes have been reported on. However, target genes identified by Pax6 knockout studies can probably be Pax6(5a) targets as well, since this isoform also will be affected by the knockout. In order to identify new Pax6 target genes, and to try to distinguish between genes regulated by Pax6 and Pax6(5a), we generated FlpIn-3T3 cell lines stably expressing Pax6 or Pax6(5a). RNA was harvested from these cell lines and used in gene expression microarrays where we identified a number of genes differentially regulated by Pax6 and Pax6(5a). A majority of these were associated with the extracellular region. By qPCR we verified that Ncam1, Ngef, Sphk1, Dkk3 and Crtap are Pax6(5a) specific target genes, while Tgfbi, Vegfa, EphB2, Klk8 and Edn1 were confirmed as Pax6 specific target genes. Nbl1, Ngfb and seven genes encoding different glycosyl transferases appeared to be regulated by both. Direct binding to the promoters of Crtap, Ctgf, Edn1, Dkk3, Pdgfb and Ngef was verified by ChIP. Furthermore, a change in morphology of the stably transfected Pax6 and Pax6(5a) cells was observed, and the Pax6 expressing cells were shown to have increased proliferation and migration capacities

Altering Chemosensitivity by Modulating Translation Elongation

BACKGROUND: The process of translation occurs at a nexus point downstream of a number of signal pathways and developmental processes. Modeling activation of the PTEN/AKT/mTOR pathway in the Emu-Myc mouse is a valuable tool to study tumor genotype/chemosensitivity relationships in vivo. In this model, blocking translation initiation with silvestrol, an inhibitor of the ribosome recruitment step has been showed to modulate the sensitivity of the tumors to the effect of standard chemotherapy. However, inhibitors of translation elongation have been tested as potential anti-cancer therapeutic agents in vitro, but have not been extensively tested in genetically well-defined mouse tumor models or for potential synergy with standard of care agents. METHODOLOGY/PRINCIPAL FINDINGS: Here, we chose four structurally different chemical inhibitors of translation elongation: homoharringtonine, bruceantin, didemnin B and cycloheximide, and tested their ability to alter the chemoresistance of Emu-myc lymphomas harbouring lesions in Pten, Tsc2, Bcl-2, or eIF4E. We show that in some genetic settings, translation elongation inhibitors are able to synergize with doxorubicin by reinstating an apoptotic program in tumor cells. We attribute this effect to a reduction in levels of pro-oncogenic or pro-survival proteins having short half-lives, like Mcl-1, cyclin D1 or c-Myc. Using lymphomas cells grown ex vivo we reproduced the synergy observed in mice between chemotherapy and elongation inhibition and show that this is reversed by blocking protein degradation with a proteasome inhibitor. CONCLUSION/SIGNIFICANCE: Our results indicate that depleting short-lived pro-survival factors by inhibiting their synthesis could achieve a therapeutic response in tumors harboring PTEN/AKT/mTOR pathway mutations

GW170104: Observation of a 50-Solar-Mass Binary Black Hole Coalescence at Redshift 0.2

We describe the observation of GW170104, a gravitational-wave signal produced by the coalescence of a pair of stellar-mass black holes. The signal was measured on January 4, 2017 at 10: 11: 58.6 UTC by the twin advanced detectors of the Laser Interferometer Gravitational-Wave Observatory during their second observing run, with a network signal-to-noise ratio of 13 and a false alarm rate less than 1 in 70 000 years. The inferred component black hole masses are 31.2(-6.0)(+8.4)M-circle dot and 19.4(-5.9)(+5.3)M(circle dot) (at the 90% credible level). The black hole spins are best constrained through measurement of the effective inspiral spin parameter, a mass-weighted combination of the spin components perpendicular to the orbital plane, chi(eff) = -0.12(-0.30)(+0.21) . This result implies that spin configurations with both component spins positively aligned with the orbital angular momentum are disfavored. The source luminosity distance is 880(-390)(+450) Mpc corresponding to a redshift of z = 0.18(-0.07)(+0.08) . We constrain the magnitude of modifications to the gravitational-wave dispersion relation and perform null tests of general relativity. Assuming that gravitons are dispersed in vacuum like massive particles, we bound the graviton mass to m(g) <= 7.7 x 10(-23) eV/c(2). In all cases, we find that GW170104 is consistent with general relativity