Fos co-operation with PTEN loss elicits keratoacanthoma not carcinoma due to p53/p21^WAF-induced differentiation triggered by GSK3b inactivation and reduced AKT activity

To investigate gene synergism in multistage skin carcinogenesis, the RU486-inducible cre/lox system was employed to ablate PTEN function [K14.cre/D5PTENflx] in mouse epidermis expressing activated v-fos [HK1.fos]. RU486-treated HK1.fos/D5PTENflx mice exhibited hyperplasia, hyperkeratosis and tumours that progressed to highly differentiated keratoacanthomas rather than carcinomas, due to re-expression of high p53 and p21WAF levels. Despite elevated MAP kinase activity, cyclin D1/E2 over expression and increased AKT activity forming areas of highly proliferative, papillomatous keratinocytes, increasing levels of GSK3b inactivation exceeded a threshold that induced p53/p21WAF expression to halt proliferation and accelerate differentiation, giving the hallmark keratosis of keratoacanthomas. A pivotal facet to this GSK3b-triggered mechanism centred on increasing p53 expression in basal layer keratinocytes. This reduced activated AKT expression and released inhibition of p21WAF, which accelerated keratinocyte differentiation, as indicated by unique basal layer expression of differentiation-specific keratin K1, alongside premature filaggrin and loricrin expression. Thus, fos synergism with PTEN loss elicited a benign tumour context where GSK3b-induced, p53/p21WAF expression continually switched AKT-associated proliferation into one of differentiation, preventing further progression. This putative compensatory mechanism required the critical availability of normal p53 and/or p21WAF otherwise deregulated fos, Akt and GSK3b associate with malignant progression

Dyson Pairs and Zero-Mass Black Holes

It has been argued by Dyson in the context of QED in flat spacetime that perturbative expansions in powers of the electric charge e cannot be convergent because if e is purely imaginary then the vacuum should be unstable to the production of charged pairs. We investigate the spontaneous production of such Dyson pairs in electrodynamics coupled to gravity. They are found to consist of pairs of zero-rest mass black holes with regular horizons. The properties of these zero rest mass black holes are discussed. We also consider ways in which a dilaton may be included and the relevance of this to recent ideas in string theory. We discuss accelerating solutions and find that, in certain circumstances, the `no strut' condition may be satisfied giving a regular solution describing a pair of zero rest mass black holes accelerating away from one another. We also study wormhole and tachyonic solutions and how they affect the stability of the vacuum.Comment: 41 pages LaTex, 5 figure

Viral Retinitis following Intraocular or Periocular Corticosteroid Administration: A Case Series and Comprehensive Review of the Literature.

Abstract Purpose: To describe viral retinitis following intravitreal and periocular corticosteroid administration. Methods: Retrospective case series and comprehensive literature review. Results: We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25-13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Conclusions: Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy

Isobutyl acetate: electronic state spectroscopy by high-resolution vacuum ultraviolet photoabsorption, He(I) photoelectron spectroscopy and ab initio calculations

The high-resolution vacuum ultraviolet photoabsorption spectrum of isobutyl acetate, C6H12O2, is presented here and was measured over the energy range 4.3–10.8 eV (290–115 nm). Valence and Rydberg transitions with their associated vibronic series have been observed in the photoabsorption spectrum and are assigned in accordance with new ab initio calculations of the vertical excitation energies and oscillator strengths. The measured photoabsorption cross sections have been used to calculate the photolysis lifetime of this ester in the Earth’s upper atmosphere (20–50 km). Calculations have also been carried out to determine the ionization energies and fine structure of the lowest ionic state of isobutyl acetate and are compared with a photoelectron spectrum (from 9.5 to 16.7 eV), recorded for the first time. Vibrational structure is observed in the first photoelectron band of this molecule

Fatigue Crack Growth Mechanisms At the Microstructure Scale in Al-Si-Mg Cast Alloys: Mechanisms in Regions II and III

The fatigue crack growth behavior in Regions 11 and III of crack growth was investigated for hypoeutectic and eutectic Al-Si-Mg cast alloys. To isolate and establish the mechanistic contributions of characteristic microstructural features (dendritic α-Al matrix, eutectic phases, Mg-Si strengthening precipitates), alloys with various Si content/morphology, grain size level, and matrix strength were studied; the effect of secondary dendrite arm spacing (SDAS) was also assessed. In Regions 11 and III of crack growth, the observed changes in the fracture surface appearance were associated with changes in crack growth mechanisms at the microstructural scale (from a linear advance predominantly through primary α-Al to a tortuous advance exclusively through AI-Si eutectic Regions). The extent of the plastic zone ahead of the crack tip was successfully used to explain the changes in growth mechanisms. The fatigue crack growth tests were conducted on compact tension specimens under constant stress ratio, R = 0.1, in ambient conditions

Regular black holes and black universes

We give a comparative description of different types of regular static, spherically symmetric black holes (BHs) and discuss in more detail their particular type, which we suggest to call black universes. The latter have a Schwarzschild-like causal structure, but inside the horizon there is an expanding Kantowski-Sachs universe and a de Sitter infinity instead of a singularity. Thus a hypothetic BH explorer gets a chance to survive. Solutions of this kind are naturally obtained if one considers static, spherically symmetric distributions of various (but not all) kinds of phantom matter whose existence is favoured by cosmological observations. It also looks possible that our Universe has originated from phantom-dominated collapse in another universe and underwent isotropization after crossing the horizon. An explicit example of a black-universe solution with positive Schwarzschild mass is discussed.Comment: 13 pages, 1 figure. 6 referenses and some discussion added, misprints correcte

Anomalous metamagnetism in the low carrier density Kondo lattice YbRh3Si7

We report complex metamagnetic transitions in single crystals of the new low carrier Kondo antiferromagnet YbRh3Si7. Electrical transport, magnetization, and specific heat measurements reveal antiferromagnetic order at T_N = 7.5 K. Neutron diffraction measurements show that the magnetic ground state of YbRh3Si7 is a collinear antiferromagnet where the moments are aligned in the ab plane. With such an ordered state, no metamagnetic transitions are expected when a magnetic field is applied along the c axis. It is therefore surprising that high field magnetization, torque, and resistivity measurements with H||c reveal two metamagnetic transitions at mu_0H_1 = 6.7 T and mu_0H_2 = 21 T. When the field is tilted away from the c axis, towards the ab plane, both metamagnetic transitions are shifted to higher fields. The first metamagnetic transition leads to an abrupt increase in the electrical resistivity, while the second transition is accompanied by a dramatic reduction in the electrical resistivity. Thus, the magnetic and electronic degrees of freedom in YbRh3Si7 are strongly coupled. We discuss the origin of the anomalous metamagnetism and conclude that it is related to competition between crystal electric field anisotropy and anisotropic exchange interactions.Comment: 23 pages and 4 figures in the main text. 7 pages and 5 figures in the supplementary materia

Near-Surface Interface Detection for Coal Mining Applications Using Bispectral Features and GPR

The use of ground penetrating radar (GPR) for detecting the presence of near-surface interfaces is a scenario of special interest to the underground coal mining industry. The problem is difficult to solve in practice because the radar echo from the near-surface interface is often dominated by unwanted components such as antenna crosstalk and ringing, ground-bounce effects, clutter, and severe attenuation. These nuisance components are also highly sensitive to subtle variations in ground conditions, rendering the application of standard signal pre-processing techniques such as background subtraction largely ineffective in the unsupervised case. As a solution to this detection problem, we develop a novel pattern recognition-based algorithm which utilizes a neural network to classify features derived from the bispectrum of 1D early time radar data. The binary classifier is used to decide between two key cases, namely whether an interface is within, for example, 5 cm of the surface or not. This go/no-go detection capability is highly valuable for underground coal mining operations, such as longwall mining, where the need to leave a remnant coal section is essential for geological stability. The classifier was trained and tested using real GPR data with ground truth measurements. The real data was acquired from a testbed with coal-clay, coal-shale and shale-clay interfaces, which represents a test mine site. We show that, unlike traditional second order correlation based methods such as matched filtering which can fail even in known conditions, the new method reliably allows the detection of interfaces using GPR to be applied in the near-surface region. In this work, we are not addressing the problem of depth estimation, rather confining ourselves to detecting an interface within a particular depth range

Neutrino Mass from R-parity Violation in Split Supersymmetry

We investigate how the observed neutrino data can be accommodated by R-parity violation in Split Supersymmetry. The atmospheric neutrino mass and mixing are explained by the bilinear parameters $\xi_i$ inducing the neutrino-neutralino mixing as in the usual low-energy supersymmetry. Among various one-loop corrections, only the quark-squark exchanging diagrams involving the order-one trilinear couplings $\lambda'_{i23,i32}$ can generate the solar neutrino mass and mixing if the scalar mass $m_S$ is not larger than $10^9$ GeV. This scheme requires an unpleasant hierarchical structure of the couplings, e.g., $\lambda_{i23,i32}\sim 1$, $\lambda'_{i33} \lesssim 10^{-4}$ and $\xi_i \lesssim 10^{-6}$. On the other hand, the model has a distinct collider signature of the lightest neutralino which can decay only to the final states, $l_i W^{(*)}$ and $\nu Z^{(*)}$, arising from the bilinear mixing. Thus, the measurement of the ratio; $\Gamma(e W^{(*)}) : \Gamma(\mu W^{(*)}) : \Gamma(\tau W^{(*)})$ would provide a clean probe of the small reactor and large atmospheric neutrino mixing angles as far as the neutralino mass is larger than 62 GeV.Comment: 10 pages, 3 figures, version submitted to JHE