Nonlinear Instability for the Critically Dissipative Quasi-Geostrophic Equation

We prove that linear instability implies non-linear instability in the energy norm for the critically dissipative quasi-geostrophic equation.Comment: 16 pages, corrected typos, a global bound that was obtained for the unforced equation by Kiselev-Nazarov-Volberg obtained for the forced equation and utilized in the paper

Einstein gravity as a 3D conformally invariant theory

We give an alternative description of the physical content of general relativity that does not require a Lorentz invariant spacetime. Instead, we find that gravity admits a dual description in terms of a theory where local size is irrelevant. The dual theory is invariant under foliation preserving 3-diffeomorphisms and 3D conformal transformations that preserve the 3-volume (for the spatially compact case). Locally, this symmetry is identical to that of Horava-Lifshitz gravity in the high energy limit but our theory is equivalent to Einstein gravity. Specifically, we find that the solutions of general relativity, in a gauge where the spatial hypersurfaces have constant mean extrinsic curvature, can be mapped to solutions of a particular gauge fixing of the dual theory. Moreover, this duality is not accidental. We provide a general geometric picture for our procedure that allows us to trade foliation invariance for conformal invariance. The dual theory provides a new proposal for the theory space of quantum gravity.Comment: 27 pages. Published version (minor changes and corrections

Lattice Kinetics of Diffusion-Limited Coalescence and Annihilation with Sources

We study the 1D kinetics of diffusion-limited coalescence and annihilation with back reactions and different kinds of particle input. By considering the changes in occupation and parity of a given interval, we derive sets of hierarchical equations from which exact expressions for the lattice coverage and the particle concentration can be obtained. We compare the mean-field approximation and the continuum approximation to the exact solutions and we discuss their regime of validity.Comment: 24 pages and 3 eps figures, Revtex, accepted for publication in J. Phys.

Estimating Nuisance Parameters in Inverse Problems

Many inverse problems include nuisance parameters which, while not of direct interest, are required to recover primary parameters. Structure present in these problems allows efficient optimization strategies - a well known example is variable projection, where nonlinear least squares problems which are linear in some parameters can be very efficiently optimized. In this paper, we extend the idea of projecting out a subset over the variables to a broad class of maximum likelihood (ML) and maximum a posteriori likelihood (MAP) problems with nuisance parameters, such as variance or degrees of freedom. As a result, we are able to incorporate nuisance parameter estimation into large-scale constrained and unconstrained inverse problem formulations. We apply the approach to a variety of problems, including estimation of unknown variance parameters in the Gaussian model, degree of freedom (d.o.f.) parameter estimation in the context of robust inverse problems, automatic calibration, and optimal experimental design. Using numerical examples, we demonstrate improvement in recovery of primary parameters for several large- scale inverse problems. The proposed approach is compatible with a wide variety of algorithms and formulations, and its implementation requires only minor modifications to existing algorithms.Comment: 16 pages, 5 figure

Radiation Damping in FRW Space-times with Different Topologies

We study the role played by the compactness and the degree of connectedness in the time evolution of the energy of a radiating system in the Friedmann-Robertson-Walker (FRW) space-times whose $t=const$ spacelike sections are the Euclidean 3-manifold ${\cal R}^3$ and six topologically non-equivalent flat orientable compact multiply connected Riemannian 3-manifolds. An exponential damping of the energy $E(t)$ is present in the ${\cal R}^3$ case, whereas for the six compact flat 3-spaces it is found basically the same pattern for the evolution of the energy, namely relative minima and maxima occurring at different times (depending on the degree of connectedness) followed by a growth of $E(t)$. Likely reasons for this divergent behavior of $E(t)$ in these compact flat 3-manifolds are discussed and further developments are indicated. A misinterpretation of Wolf's results regarding one of the six orientable compact flat 3-manifolds is also indicated and rectified.Comment: 13 pages, RevTeX, 5 figures, To appear in Phys. Rev. D 15, vol. 57 (1998

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial

© Cuzick et al. Open Access article distributed under the terms of CC BY.http://dx.doi.org/10.1016/S1470-2045(14)71171-

Discovery of Novel MicroRNAs in Rat Kidney Using Next Generation Sequencing and Microarray Validation

MicroRNAs (miRNAs) are small non-coding RNAs that regulate a variety of biological processes. The latest version of the miRBase database (Release 18) includes 1,157 mouse and 680 rat mature miRNAs. Only one new rat mature miRNA was added to the rat miRNA database from version 16 to version 18 of miRBase, suggesting that many rat miRNAs remain to be discovered. Given the importance of rat as a model organism, discovery of the completed set of rat miRNAs is necessary for understanding rat miRNA regulation. In this study, next generation sequencing (NGS), microarray analysis and bioinformatics technologies were applied to discover novel miRNAs in rat kidneys. MiRanalyzer was utilized to analyze the sequences of the small RNAs generated from NGS analysis of rat kidney samples. Hundreds of novel miRNA candidates were examined according to the mappings of their reads to the rat genome, presence of sequences that can form a miRNA hairpin structure around the mapped locations, Dicer cleavage patterns, and the levels of their expression determined by both NGS and microarray analyses. Nine novel rat hairpin precursor miRNAs (pre-miRNA) were discovered with high confidence. Five of the novel pre-miRNAs are also reported in other species while four of them are rat specific. In summary, 9 novel pre-miRNAs (14 novel mature miRNAs) were identified via combination of NGS, microarray and bioinformatics high-throughput technologies

Molecular Evolution of Lepidopteran Silk Proteins: Insights from the Ghost Moth, Hepialus californicus

Silk production has independently evolved in numerous arthropod lineages, such as Lepidoptera, the moths and butterflies. Lepidopteran larvae (caterpillars) synthesize silk proteins in modified salivary glands and spin silk fibers into protective tunnels, escape lines, and pupation cocoons. Molecular sequence data for these proteins are necessary to determine critical features of their function and evolution. To this end, we constructed an expression library from the silk glands of the ghost moth, Hepialus californicus, and characterized light chainfibroin and heavy chain fibroin gene transcripts. The predicted H. californicus silk fibroins share many elements with other lepidopteran and trichopteran fibroins, such as conserved placements of cysteine, aromatic, and polar amino acid residues. Further comparative analyses were performed to determine site-specific signatures of selection and to assess whether fibroin genes are informative as phylogenetic markers. We found that purifying selection has constrained mutation within the fibroins and that light chain fibroin is a promising molecular marker. Thus, by characterizing the H. californicus fibroins, we identified key functional amino acids and gained insight into the evolutionary processes that have shaped these adaptive molecules

Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo

Introduction Trastuzumab is widely used for the treatment of HER2-positive breast cancer. Despite encouraging clinical results, a significant fraction of patients are, or become, refractory to the drug. To overcome this, trastuzumab-DM1 (T-DM1), a newer, more potent drug has been introduced. We tested the efficacy and mechanisms of action of T-DM1 in nine HER2-positive breast cancer cell lines in vitro and in vivo. The nine cell lines studied included UACC-893, MDA-453 and JIMT-1, which are resistant to both trastuzumab and lapatinib. Methods AlamarBlue cell-proliferation assay was used to determine the growth response of breast cancer cell lines to trastuzumab and T-DM1 in vitro. Trastuzumab- and T-DM1-mediated antibody-dependent cellular cytotoxicity (ADCC) was analysed by measuring the lactate dehydrogenase released from the cancer cells as a result of ADCC activity of peripheral blood mononuclear cells. Severe Combined Immunodeficient (SCID) mice were inoculated with trastuzumab-resistant JIMT-1 cells to investigate the tumour inhibitory effect of T-DM1 in vivo. The xenograft samples were investigated using histology and immunohistochemistry. Results T-DM1 was strongly growth inhibitory on all investigated HER2-positive breast cancer cell lines in vitro. T-DM1 also evoked antibody-dependent cellular cytotoxicity (ADCC) similar to that of trastuzumab. Outgrowth of JIMT-1 xenograft tumours in SCID mice was significantly inhibited by T-DM1. Histologically, the cellular response to T-DM1 consisted of apoptosis and mitotic catastrophe, the latter evidenced by an increased number of cells with aberrant mitotic figures and giant multinucleated cells. Conclusions Our results suggest mitotic catastrophe as a previously undescribed mechanism of action of T-DM1. T-DM1 was found effective even on breast cancer cell lines with moderate HER2 expression levels and cross-resistance to trastuzumab and lapatinib (MDA-453 and JIMT-1).BioMed Central Open acces