Non-perturbative QEG Corrections to the Yang-Mills Beta Function

We discuss the non-perturbative renormalization group evolution of the gauge coupling constant by using a truncated form of the functional flow equation for the effective average action of the Yang-Mills-gravity system. Our result is consistent with the conjecture that Quantum Einstein Gravity (QEG) is asymptotically safe and has a vanishing gauge coupling constant at the non-trivial fixed point.Comment: To appear in the proceedings of CORFU 200

Abundance and evolution of galaxy clusters in cosmological models with massive neutrino

The time evolution of the number density of galaxy clusters and their mass and temperature functions are used to constrain cosmological parameters in the spatially flat dark matter models containing a fraction of hot particles (massive neutrino) additional to cold and baryonic matter. We test the modified MDM models with cosmic gravitational waves and show that they neither pass the cluster evolution test nor reproduce the observed height of the first acoustic peak in $\Delta T/T$ spectrum, and therefore should be ruled out. The models with a non-zero cosmological constant are in better agreement with observations. We estimate the free cosmological parameters in $\Lambda$MDM with a negligible abundance of gravitational waves, and find that within the parameter ranges $h\in (0.6, 0.7)$, $n\in (0.9, 1.1)$, (i) the value of $\Omega_\Lambda$ is strongly affected by a small fraction of hot dark matter, $f_\nu\equiv\Omega_\nu /\Omega_m\in (0, 0.2)$: $0.45 <\Omega_\Lambda <0.7$ ($1\sigma$ CL), and (ii) the redshift evolution of galaxy clusters alone reveals the following explicit correlation between $\Omega_\Lambda$ and $f_\nu$: $\Omega_\Lambda +0.5f_\nu =0.65\pm 0.1$. The present accuracy of observational data allows only to bound the fraction of hot matter, $f_\nu\in (0, 0.2)$ (the number of massive neutrino species remains undelimited, $N_\nu =1, 2, 3$).Comment: 9 pages, 7 figures, submitted in A&

Rapid modification of the bone microenvironment following short-term treatment with Cabozantinib in vivo

Introduction: Bone metastasis remains incurable with treatment restricted to palliative care. Cabozantinib (CBZ) is targeted against multiple receptor tyrosine kinases involved in tumour pathobiology, including hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR-2). CBZ has demonstrated clinical activity in advanced prostate cancer with resolution of lesions visible on bone scans, implicating a potential role of the bone microenvironment as a mediator of CBZ effects. We characterised the effects of short-term administration of CBZ on bone in a range of in vivo models to determine how CBZ affects bone in the absence of tumour. Methods: Studies were performed in a variety of in vivo models including male and female BALB/c nude mice (age 6– 17-weeks). Animals received CBZ (30 mg/kg, 5× weekly) or sterile H2O control for 5 or 10 days. Effects on bone integrity (μCT), bone cell activity (PINP, TRAP ELISA), osteoblast and osteoclast number/mm trabecular bone surface, area of epiphyseal growth plate cartilage, megakaryocyte numbers and bone marrow composition were assessed. Effects of longer-term treatment (15-day & 6-week administration) were assessed in male NOD/SCID and beige SCID mice. Results: CBZ treatment had significant effects on the bone microenvironment, including reduced osteoclast and increased osteoblast numbers compared to control. Trabecular bone structure was altered after 8 administrations. A significant elongation of the epiphyseal growth plate, in particular the hypertrophic chondrocyte zone, was observed in all CBZ treated animals irrespective of administration schedule. Both male and female BALB/c nude mice had increased megakaryocyte numbers/mm2 tissue after 10-day CBZ treatment, in addition to vascular ectasia, reduced bone marrow cellularity and extravasation of red blood cells into the extra-vascular bone marrow. All CBZinduced effects were transient and rapidly lost following cessation of treatment. Conclusion: Short-term administration of CBZ induces rapid, reversible effects on the bone microenvironmentin vivo highlighting a potential role in mediating treatment responses

Genome editing poses ethical problems that we cannot ignore

The ability to precisely and accurately change almost any part of any genome, even in complex species such as humans, may soon become a reality through genome editing. But with great power comes great responsibility – and few subjects elicit such heated debates about moral rights and wrongs. Although genetic engineering techniques have been around for some time, genome editing can achieve this with lower error rates, more simply and cheaply than ever – although the technology is certainly not yet perfect. Genome editing offers a greater degree of control and precision in how specific DNA sequences are changed. It could be used in basic science, for human health, or improvements to crops. There are a variety of techniques but clustered regularly inter-spaced short palindromic repeats, or CRISPR, is perhaps the foremost. CRISPR has prompted recent calls for a genome editing moratorium from a group of concerned US academics. Because it is the easiest technique to set up and so could be quickly and widely adopted, the fear is that it may be put into use far too soon – outstripping our understanding of its safety implications and preventing any opportunity to think about how such powerful tools should be controlled. Ethical concerns over genetic modification are not new, particularly when it comes to humans. While we don’t think genome editing gives rise to any completely new ethical concerns, there is more to gene editing than just genetic modification..

Towards a formalism for mapping the spacetimes of massive compact objects: Bumpy black holes and their orbits

Observations have established that extremely compact, massive objects are common in the universe. It is generally accepted that these objects are black holes. As observations improve, it becomes possible to test this hypothesis in ever greater detail. In particular, it is or will be possible to measure the properties of orbits deep in the strong field of a black hole candidate (using x-ray timing or with gravitational-waves) and to test whether they have the characteristics of black hole orbits in general relativity. Such measurements can be used to map the spacetime of a massive compact object, testing whether the object's multipoles satisfy the strict constraints of the black hole hypothesis. Such a test requires that we compare against objects with the ``wrong'' multipole structure. In this paper, we present tools for constructing bumpy black holes: objects that are almost black holes, but that have some multipoles with the wrong value. The spacetimes which we present are good deep into the strong field of the object -- we do not use a large r expansion, except to make contact with weak field intuition. Also, our spacetimes reduce to the black hole spacetimes of general relativity when the ``bumpiness'' is set to zero. We propose bumpy black holes as the foundation for a null experiment: if black hole candidates are the black holes of general relativity, their bumpiness should be zero. By comparing orbits in a bumpy spacetime with those of an astrophysical source, observations should be able to test this hypothesis, stringently testing whether they are the black holes of general relativity. (Abridged)Comment: 16 pages + 2 appendices + 3 figures. Submitted to PR

Covariant anomaly and Hawking radiation from the modified black hole in the rainbow gravity theory

Recently, Banerjee and Kulkarni (R. Banerjee, S. Kulkarni, arXiv:0707.2449 [hep-th]) suggested that it is conceptually clean and economical to use only the covariant anomaly to derive Hawking radiation from a black hole. Based upon this simplified formalism, we apply the covariant anomaly cancellation method to investigate Hawking radiation from a modified Schwarzschild black hole in the theory of rainbow gravity. Hawking temperature of the gravity's rainbow black hole is derived from the energy-momentum flux by requiring it to cancel the covariant gravitational anomaly at the horizon. We stress that this temperature is exactly the same as that calculated by the method of cancelling the consistent anomaly.Comment: 5 page

MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma

This study investigates the influence expression of the MYCN oncogene has on the DNA damage response, replication fork progression and sensitivity to PARP inhibition in neuroblastoma. In a panel of neuroblastoma cell lines, MYCN amplification or MYCN expression resulted in increased cell death in response to a range of PARP inhibitors (niraparib, veliparib, talazoparib and olaparib) compared to the response seen in non-expressing/amplified cells. MYCN expression slowed replication fork speed and increased replication fork stalling, an effect that was amplified by PARP inhibition or PARP1 depletion. Increased DNA damage seen was specifically induced in S-phase cells. Importantly, PARP inhibition caused a significant increase in the survival of mice bearing MYCN expressing tumours in a transgenic murine model of MYCN expressing neuroblastoma. Olaparib also sensitized MYCN expressing cells to camptothecin- and temozolomide-induced cell death to a greater degree than non-expressing cells. In summary, MYCN expression leads to increased replication stress in neuroblastoma cells. This effect is exaggerated by inhibition of PARP, resulting in S-phase specific DNA damage and ultimately increased tumour cell death. PARP inhibition alone or in combination with classical chemotherapeutics is therefore a potential therapeutic strategy for neuroblastoma and may be more effective in MYCN expressing tumours

A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping

SummaryWe use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs “facing” one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.PaperFlic

Black Hole Entropy: From Shannon to Bekenstein

In this note we have applied directly the Shannon formula for information theory entropy to derive the Black Hole (Bekenstein-Hawking) entropy. Our analysis is semi-classical in nature since we use the (recently proposed [8]) quantum mechanical near horizon mode functions to compute the tunneling probability that goes in to the Shannon formula, following the general idea of [5]. Our framework conforms to the information theoretic origin of Black Hole entropy, as originally proposed by Bekenstein.Comment: 9 pages Latex, Comments are welcome; Thoroughly revised version, reference and acknowledgements sections enlarged, numerical error in final result corrected, no major changes, to appear in IJT