1,598 research outputs found

    mTORC2 signaling drives the development and progression of pancreatic cancer

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    mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer

    Testing "microscopic" theories of glass-forming liquids

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    We assess the validity of "microscopic" approaches of glass-forming liquids based on the sole k nowledge of the static pair density correlations. To do so we apply them to a benchmark provided by two liquid models that share very similar static pair density correlation functions while disp laying distinct temperature evolutions of their relaxation times. We find that the approaches are unsuccessful in describing the difference in the dynamical behavior of the two models. Our study is not exhausti ve, and we have not tested the effect of adding corrections by including for instance three-body density correlations. Yet, our results appear strong enough to challenge the claim that the slowd own of relaxation in glass-forming liquids, for which it is well established that the changes of the static structure factor with temperature are small, can be explained by "microscopic" appr oaches only requiring the static pair density correlations as nontrivial input.Comment: 10 pages, 7 figs; Accepted to EPJE Special Issue on The Physics of Glasses. Arxiv version contains an addendum to the appendix which does not appear in published versio

    Softening the Supersymmetric Flavor Problem in Orbifold GUTs

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    The infra-red attractive force of the bulk gauge interactions is applied to soften the supersymmetric flavor problem in the orbifold SU(5) GUT of Kawamura. Then this force aligns in the infra-red regime the soft supersymmetry breaking terms out of their anarchical disorder at a fundamental scale, in such a way that flavor-changing neutral currents as well as dangerous CP-violating phases are suppressed at low energies. It is found that this dynamical alignment is sufficiently good compared with the current experimental bounds, as long as the diagonalization matrices of the Yukawa couplings are CKM-like.Comment: 15 pages,4 figure

    Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging

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    We present a measurement of the top quark pair (ttˉt\bar{t}) production cross section (σttˉ\sigma_{t\bar{t}}) in ppˉp\bar{p} collisions at s=1.96\sqrt{s}=1.96 TeV using 230 pb1^{-1} of data collected by the D0 experiment at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), missing transverse energy, and jets in the final state. We employ lifetime-based b-jet identification techniques to further enhance the ttˉt\bar{t} purity of the selected sample. For a top quark mass of 175 GeV, we measure σttˉ=8.61.5+1.6(stat.+syst.)±0.6(lumi.)\sigma_{t\bar{t}}=8.6^{+1.6}_{-1.5}(stat.+syst.)\pm 0.6(lumi.) pb, in agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let

    A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses

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    We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants

    b-Jet Identification in the D0 Experiment

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    Algorithms distinguishing jets originating from b quarks from other jet flavors are important tools in the physics program of the D0 experiment at the Fermilab Tevatron p-pbar collider. This article describes the methods that have been used to identify b-quark jets, exploiting in particular the long lifetimes of b-flavored hadrons, and the calibration of the performance of these algorithms based on collider data.Comment: submitted to Nuclear Instruments and Methods in Physics Research

    Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

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    The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review
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