Reference frames and rigid motions in relativity: Applications

The concept of rigid reference frame and of constricted spatial metric, given in the previous work [\emph{Class. Quantum Grav.} {\bf 21}, 3067,(2004)] are here applied to some specific space-times: In particular, the rigid rotating disc with constant angular velocity in Minkowski space-time is analyzed, a new approach to the Ehrenfest paradox is given as well as a new explanation of the Sagnac effect. Finally the anisotropy of the speed of light and its measurable consequences in a reference frame co-moving with the Earth are discussed.Comment: 13 pages, 1 figur

The Role of Calcineurin/NFAT in SFRP2 Induced Angiogenesis—A Rationale for Breast Cancer Treatment with the Calcineurin Inhibitor Tacrolimus

Tacrolimus (FK506) is an immunosuppressive drug that binds to the immunophilin FKBPB12. The FK506-FKBP12 complex associates with calcineurin and inhibits its phosphatase activity, resulting in inhibition of nuclear translocation of nuclear factor of activated T-cells (NFAT). There is increasing data supporting a critical role of NFAT in mediating angiogenic responses stimulated by both vascular endothelial growth factor (VEGF) and a novel angiogenesis factor, secreted frizzled-related protein 2 (SFRP2). Since both VEGF and SFRP2 are expressed in breast carcinomas, we hypothesized that tacrolimus would inhibit breast carcinoma growth. Using IHC (IHC) with antibodies to FKBP12 on breast carcinomas we found that FKBP12 localizes to breast tumor vasculature. Treatment of MMTV-neu transgenic mice with tacrolimus (3 mg/kg i.p. daily) (n = 19) resulted in a 73% reduction in the growth rate for tacrolimus treated mice compared to control (n = 15), p = 0.003; which was associated with an 82% reduction in tumor microvascular density (p<0.001) by IHC. Tacrolimus (1 µM) inhibited SFRP2 induced endothelial tube formation by 71% (p = 0.005) and inhibited VEGF induced endothelial tube formation by 67% (p = 0.004). To show that NFATc3 is required for SFRP2 stimulated angiogenesis, NFATc3 was silenced with shRNA in endothelial cells. Sham transfected cells responded to SFRP2 stimulation in a tube formation assay with an increase in the number of branch points (p<0.003), however, cells transfected with shRNA to NFATc3 showed no increase in tube formation in response to SFRP2. This demonstrates that NFATc3 is required for SFRP2 induced tube formation, and tacrolimus inhibits angiogenesis in vitro and breast carcinoma growth in vivo. This provides a rationale for examining the therapeutic potential of tacrolimus at inhibiting breast carcinoma growth in humans

Locality hypothesis and the speed of light

The locality hypothesis is generally considered necessary for the study of the kinematics of non-inertial systems in special relativity. In this paper we discuss this hypothesis, showing the necessity of an improvement, in order to get a more clear understanding of the various concepts involved, like coordinate velocity and standard velocity of light. Concrete examples are shown, where these concepts are discussed.Comment: 23 page

On the experimental determination of the one-way speed of light

In this contribution the question of the isotropy of the one-way speed of light from an experimental perspective is addressed. In particular, we analyze two experimental methods commonly used in its determination. The analysis is aimed at clarifying the view that the one-way speed of light cannot be determined by techniques in which physical entities close paths. The procedure employed here will provide epistemological tools such that physicists understand that a direct measurement of the speed not only of light but of any physical entity is by no means trivial. Our results shed light on the physics behind the experiments which may be of interest for both physicists with an elemental knowledge in special relativity and philosophers of science.Comment: 8 pages, 5 figures. To appear in the European Journal of Physic

The relativistic Sagnac Effect: two derivations

The phase shift due to the Sagnac Effect, for relativistic matter and electromagnetic beams, counter-propagating in a rotating interferometer, is deduced using two different approaches. From one hand, we show that the relativistic law of velocity addition leads to the well known Sagnac time difference, which is the same independently of the physical nature of the interfering beams, evidencing in this way the universality of the effect. Another derivation is based on a formal analogy with the phase shift induced by the magnetic potential for charged particles travelling in a region where a constant vector potential is present: this is the so called Aharonov-Bohm effect. Both derivations are carried out in a fully relativistic context, using a suitable 1+3 splitting that allows us to recognize and define the space where electromagnetic and matter waves propagate: this is an extended 3-space, which we call "relative space". It is recognized as the only space having an actual physical meaning from an operational point of view, and it is identified as the 'physical space of the rotating platform': the geometry of this space turns out to be non Euclidean, according to Einstein's early intuition.Comment: 49 pages, LaTeX, 3 EPS figures. Revised (final) version, minor corrections; to appear in "Relativity in Rotating Frames", ed. G. Rizzi and M.L. Ruggiero, Kluwer Academic Publishers, Dordrecht, (2003). See also http://digilander.libero.it/solciclo

Simultaneity and generalized connections in general relativity

Stationary extended frames in general relativity are considered. The requirement of stationarity allows to treat the spacetime as a principal fiber bundle over the one-dimensional group of time translations. Over this bundle a connection form establishes the simultaneity between neighboring events accordingly with the Einstein synchronization convention. The mathematics involved is that of gauge theories where a gauge choice is interpreted as a global simultaneity convention. Then simultaneity in non-stationary frames is investigated: it turns to be described by a gauge theory in a fiber bundle without structure group, the curvature being given by the Fr\"olicher-Nijenhuis bracket of the connection. The Bianchi identity of this gauge theory is a differential relation between the vorticity field and the acceleration field. In order for the simultaneity connection to be principal, a necessary and sufficient condition on the 4-velocity of the observers is given.Comment: RevTeX, 9 pages, 2 figures, 1 table. Previous title "The gauge nature of simultaneity". Classical and Quantum Gravity http://www.iop.org/EJ/journal/CQ

Performance bounds on compressed sensing with Poisson noise

This paper describes performance bounds for compressed sensing in the presence of Poisson noise when the underlying signal, a vector of Poisson intensities, is sparse or compressible (admits a sparse approximation). The signal-independent and bounded noise models used in the literature to analyze the performance of compressed sensing do not accurately model the effects of Poisson noise. However, Poisson noise is an appropriate noise model for a variety of applications, including low-light imaging, where sensing hardware is large or expensive, and limiting the number of measurements collected is important. In this paper, we describe how a feasible positivity-preserving sensing matrix can be constructed, and then analyze the performance of a compressed sensing reconstruction approach for Poisson data that minimizes an objective function consisting of a negative Poisson log likelihood term and a penalty term which could be used as a measure of signal sparsity.Comment: 5 pages; to appear in Proc. ISIT 200

Genetic Variants of VEGFA and FLT4 Are Determinants of Survival in Renal Cell Carcinoma Patients Treated with Sorafenib

Molecular markers of sorafenib efficacy in patients with metastatic renal cell carcinoma (mRCC) are not available. The purpose of this study was to discover genetic markers of survival in patients with mRCC treated with sorafenib. Germline variants from 56 genes were genotyped in 295 patients with mRCC. Variant-overall survival (OS) associations were tested in multivariate regression models. Mechanistic studies were conducted to validate clinical associations. VEGFA rs1885657, ITGAV rs3816375, and WWOX rs8047917 (sorafenib arm), and FLT4 rs307826 and VEGFA rs3024987 (sorafenib and placebo arms combined) were associated with shorter OS. FLT4 rs307826 increased VEGFR-3 phosphorylation, membrane trafficking, and receptor activation. VEGFA rs1885657 and rs58159269 increased transcriptional activity of the constructs containing these variants in endothelial and RCC cell lines, and VEGFA rs58159269 increased endothelial cell proliferation and tube formation. FLT4 rs307826 and VEGFA rs58159269 led to reduced sorafenib cytotoxicity. Genetic variation in VEGFA and FLT4 could affect survival in sorafenib-treated patients with mRCC. These markers should be examined in additional malignancies treated with sorafenib and in other angiogenesis inhibitors used in mRCC. Significance: Clinical and mechanistic data identify germline genetic variants in VEGFA and FLT4 as markers of survival in patients with metastatic renal cell carcinoma.Peer reviewe

Using batch reactor results to calculate optimal flow rates for the scale-up of UV photochemical reactions

The perceived difficulty of the scale-up of photochemistry is one of the main obstacles preventing its widespread use. Herein, we take three different challenging reactions and show that they can be reliably scaled, from immersion well batch reactors to higher power FEP flow reactors. Key to the success has been the development of a powerful calculation methodology which enables the accurate calculation of reactor flow rates from these and previously optimised batch reactions. Despite the challenging nature of these systems, in all cases tens of grams of material was obtained

Environmental Impact on Vascular Development Predicted by High-Throughput Screening

Background: Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High-throughput screening (HTS) in the U.S. Environmental Protection Agency (EPA) ToxCast™ project provides vast data on an expanding chemical library currently consisting of > 1,000 unique compounds across > 500 in vitro assays in phase I (complete) and Phase II (under way). This public data set can be used to evaluate concentration-dependent effects on many diverse biological targets and build predictive models of prototypical toxicity pathways that can aid decision making for assessments of human developmental health and disease