Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly

Energy Density of Non-Minimally Coupled Scalar Field Cosmologies

Scalar fields coupled to gravity via $\xi R {\Phi}^2$ in arbitrary Friedmann-Robertson-Walker backgrounds can be represented by an effective flat space field theory. We derive an expression for the scalar energy density where the effective scalar mass becomes an explicit function of $\xi$ and the scale factor. The scalar quartic self-coupling gets shifted and can vanish for a particular choice of $\xi$. Gravitationally induced symmetry breaking and de-stabilization are possible in this theory.Comment: 18 pages in standard Late

Geometric structure of the generic static traversable wormhole throat

Traversable wormholes have traditionally been viewed as intrinsically topological entities in some multiply connected spacetime. Here, we show that topology is too limited a tool to accurately characterize a generic traversable wormhole: in general one needs geometric information to detect the presence of a wormhole, or more precisely to locate the wormhole throat. For an arbitrary static spacetime we shall define the wormhole throat in terms of a 2-dimensional constant-time hypersurface of minimal area. (Zero trace for the extrinsic curvature plus a "flare-out" condition.) This enables us to severely constrain the geometry of spacetime at the wormhole throat and to derive generalized theorems regarding violations of the energy conditions-theorems that do not involve geodesic averaging but nevertheless apply to situations much more general than the spherically symmetric Morris-Thorne traversable wormhole. [For example: the null energy condition (NEC), when suitably weighted and integrated over the wormhole throat, must be violated.] The major technical limitation of the current approach is that we work in a static spacetime-this is already a quite rich and complicated system.Comment: 25 pages; plain LaTeX; uses epsf.sty (four encapsulated postscript figures

Overestimating the Role of Environment in Cancers

In a recent article, Wu and colleagues (Nature 2016;529:43-47) review previous studies and present new estimates for the contribution of extrinsic factors to cancer development. The new estimates are generally close to 100%, even for bone and brain cancers that have no known associations with lifestyle and are typically not considered to be preventable. We find that the results of Wu and colleagues are incompatible with previous estimates derived from epidemiological and genetic data. We further argue that their methods are fundamentally flawed because they overlook important effects of tissue type on cancer risk. We therefore conclude that their results give a misleading view of cancer etiology and preventability. Cancer Prev Res; 9(10); 773-6. ©2016 AACR

Tolman wormholes violate the strong energy condition

For an arbitrary Tolman wormhole, unconstrained by symmetry, we shall define the bounce in terms of a three-dimensional edgeless achronal spacelike hypersurface of minimal volume. (Zero trace for the extrinsic curvature plus a "flare-out" condition.) This enables us to severely constrain the geometry of spacetime at and near the bounce and to derive general theorems regarding violations of the energy conditions--theorems that do not involve geodesic averaging but nevertheless apply to situations much more general than the highly symmetric FRW-based subclass of Tolman wormholes. [For example: even under the mildest of hypotheses, the strong energy condition (SEC) must be violated.] Alternatively, one can dispense with the minimal volume condition and define a generic bounce entirely in terms of the motion of test particles (future-pointing timelike geodesics), by looking at the expansion of their timelike geodesic congruences. One re-confirms that the SEC must be violated at or near the bounce. In contrast, it is easy to arrange for all the other standard energy conditions to be satisfied.Comment: 8 pages, ReV-TeX 3.

Heat kernel regularization of the effective action for stochastic reaction-diffusion equations

The presence of fluctuations and non-linear interactions can lead to scale dependence in the parameters appearing in stochastic differential equations. Stochastic dynamics can be formulated in terms of functional integrals. In this paper we apply the heat kernel method to study the short distance renormalizability of a stochastic (polynomial) reaction-diffusion equation with real additive noise. We calculate the one-loop {\emph{effective action}} and its ultraviolet scale dependent divergences. We show that for white noise a polynomial reaction-diffusion equation is one-loop {\emph{finite}} in $d=0$ and $d=1$, and is one-loop renormalizable in $d=2$ and $d=3$ space dimensions. We obtain the one-loop renormalization group equations and find they run with scale only in $d=2$.Comment: 21 pages, uses ReV-TeX 3.

Vacuum decay via Lorentzian wormholes

We speculate about the spacetime description due to the presence of Lorentzian wormholes (handles in spacetime joining two distant regions or other universes) in quantum gravity. The semiclassical rate of production of these Lorentzian wormholes in Reissner-Nordstr\"om spacetimes is calculated as a result of the spontaneous decay of vacuum due to a real tunneling configuration. In the magnetic case it only depends on the field theoretical fine structure constant. We predict that the quantum probability corresponding to the nucleation of such geodesically complete spacetimes should be actually negligible in our physical Universe

<Tνμ>ren<T^{\mu}_{\nu}>_{ren} of the quantized fields in the Unruh state in the Schwarzschild spacetime

The renormalized expectation value of the stress energy tensor of the conformally invariant massless fields in the Unruh state in the Schwarzschild spacetime is constructed. It is achieved through solving the conservation equation in conformal space and utilizing the regularity conditions in the physical metric. The relations of obtained results to the existing approximations are analysed.Comment: 17 pages, REVTE

Semiclassical charged black holes with a quantized massive scalar field

Semiclassical perturbations to the Reissner-Nordstrom metric caused by the presence of a quantized massive scalar field with arbitrary curvature coupling are found to first order in \epsilon = \hbar/M^2. The DeWitt-Schwinger approximation is used to determine the vacuum stress-energy tensor of the massive scalar field. When the semiclassical perturbation are taken into account, we find extreme black holes will have a charge-to-mass ratio that exceeds unity, as measured at infinity. The effects of the perturbations on the black hole temperature (surface gravity) are studied in detail, with particular emphasis on near extreme ``bare'' states that might become precisely zero temperature ``dressed'' semiclassical black hole states. We find that for minimally or conformally coupled scalar fields there are no zero temperature solutions among the perturbed black holes.Comment: 19 pages; 1 figure; ReVTe