Grainyhead-like 2 (GRHL2) knockout abolishes oral cancer development through reciprocal regulation of the MAP kinase and TGF-β signaling pathways

Grainyhead-Like 2 (GRHL2) is an epithelial-specific transcription factor that regulates epithelial morphogenesis and differentiation. Prior studies suggested inverse regulation between GRHL2 and TGF-β in epithelial plasticity and potential carcinogenesis. Here, we report the role of GRHL2 in oral carcinogenesis in vivo using a novel Grhl2 knockout (KO) mouse model and the underlying mechanism involving its functional interaction with TGF-β signaling. We developed epithelial-specific Grhl2 conditional KO mice by crossing Grhl2 floxed mice with those expressing CreER driven by the K14 promoter. After induction of Grhl2 KO, we confirmed the loss of GRHL2 and its target proteins, while Grhl2 KO strongly induced TGF-β signaling molecules. When exposed to 4-nitroquinoline 1-oxide (4-NQO), a strong chemical carcinogen, Grhl2 wild-type (WT) mice developed rampant oral tongue tumors, while Grhl2 KO mice completely abolished tumor development. In cultured oral squamous cell carcinoma (OSCC) cell lines, TGF-β signaling was notably induced by GRHL2 knockdown while being suppressed by GRHL2 overexpression. GRHL2 knockdown or KO in vitro and in vivo, respectively, led to loss of active p-Erk1/2 and p-JNK MAP kinase levels; moreover, ectopic overexpression of GRHL2 strongly induced the MAP kinase activation. Furthermore, the suppressive effect of GRHL2 on TGF-β signaling was diminished in cells exposed to Erk and JNK inhibitors. These data indicate that GRHL2 activates the Erk and JNK MAP kinases, which in turn suppresses the TGF -β signaling. This novel signaling represents an alternative pathway by which GRHL2 regulates carcinogenesis, and is distinct from the direct transcriptional regulation by GRHL2 binding at its target gene promoters, e.g., E-cadherin, hTERT, p63, and miR-200 family genes. Taken together, the current study provides the first genetic evidence to support the role of GRHL2 in carcinogenesis and the underlying novel mechanism that involves the functional interaction between GRHL2 and TGF-β signaling through the MAPK pathways

Performance of the CREAM calorimeter in accelerator beam test

The CREAM calorimeter, designed to measure the spectra of cosmic-ray nuclei from under 1 TeV to 1000 TeV, is a 20 radiation length (X0) deep sampling calorimeter. The calorimeter is comprised of 20 layers of tungsten interleaved with 20 layers of scintillating fiber ribbons, and is preceded by a pair of graphite interaction targets providing about 0.42 proton interaction lengths (\lambda int). The calorimeter was placed in one of CERN's SPS accelerator beams for calibration and testing. Beams of 150 GeV electrons were used for calibration, and a variety of electron, proton, and nuclear fragment beams were used to test the simulation model of the detector. In this paper we discuss the performance of the calorimeter in the electron beam and compare electron beam data with simulation results.The CREAM calorimeter, designed to measure the spectra of cosmic-ray nuclei from under 1 TeV to 1000 TeV, is a 20 radiation length (X0) deep sampling calorimeter. The calorimeter is comprised of 20 layers of tungsten interleaved with 20 layers of scintillating fiber ribbons, and is preceded by a pair of graphite interaction targets providing about 0.42 proton interaction lengths (\lambda int). The calorimeter was placed in one of CERN's SPS accelerator beams for calibration and testing. Beams of 150 GeV electrons were used for calibration, and a variety of electron, proton, and nuclear fragment beams were used to test the simulation model of the detector. In this paper we discuss the performance of the calorimeter in the electron beam and compare electron beam data with simulation results

Klein tunneling in graphene: optics with massless electrons

This article provides a pedagogical review on Klein tunneling in graphene, i.e. the peculiar tunneling properties of two-dimensional massless Dirac electrons. We consider two simple situations in detail: a massless Dirac electron incident either on a potential step or on a potential barrier and use elementary quantum wave mechanics to obtain the transmission probability. We emphasize the connection to related phenomena in optics, such as the Snell-Descartes law of refraction, total internal reflection, Fabry-P\'erot resonances, negative refraction index materials (the so called meta-materials), etc. We also stress that Klein tunneling is not a genuine quantum tunneling effect as it does not necessarily involve passing through a classically forbidden region via evanescent waves. A crucial role in Klein tunneling is played by the conservation of (sublattice) pseudo-spin, which is discussed in detail. A major consequence is the absence of backscattering at normal incidence, of which we give a new shorten proof. The current experimental status is also thoroughly reviewed. The appendix contains the discussion of a one-dimensional toy model that clearly illustrates the difference in Klein tunneling between mono- and bi-layer graphene.Comment: short review article, 18 pages, 14 figures; v3: references added, several figures slightly modifie

Anti-biofouling implantable catheter using thin-film magnetic microactuators

Here we report on the development of polyimide-based flexible magnetic actuators for actively combating biofouling that occurs in many chronically implanted devices. The thin-film flexible devices are microfabricated and integrated into a single-pore silicone catheter to demonstrate a proof-of-concept for a self-clearing smart catheter. The static and dynamic mechanical responses of the thin-film magnetic microdevices were quantitatively measured and compared to theoretical values. The mechanical fatigue properties of these polyimide-based microdevices were also characterized up to 300 million cycles. Finally, the biofouling removal capabilities of magnetically powered microdevices were demonstrated using bovine serum albumin and bioconjugated microbeads. Our results indicate that these thin-film microdevices are capable of significantly reducing the amount of biofouling. At the same time, we demonstrated that these microdevices are mechanically robust enough to withstand a large number of actuation cycles during its chronic implantation

Antiferromagnetic Domains and Superconductivity in UPt3

We explore the response of an unconventional superconductor to spatially inhomogeneous antiferromagnetism (SIAFM). Symmetry allows the superconducting order parameter in the E-representation models for UPt3 to couple directly to the AFM order parameter. The Ginzburg-Landau equations for coupled superconductivity and SIAFM are solved numerically for two possible SIAFM configurations: (I) abutting antiferromagnetic domains of uniform size, and (II) quenched random disorder of `nanodomains' in a uniform AFM background. We discuss the contributions to the free energy, specific heat, and order parameter for these models. Neither model provides a satisfactory account of experiment, but results from the two models differ significantly. Our results demonstrate that the response of an E_{2u} superconductor to SIAFM is strongly dependent on the spatial dependence of AFM order; no conclusion can be drawn regarding the compatibility of E_{2u} superconductivity with UPt3 that is independent of assumptions on the spatial dependence of AFMComment: 12 pages, 13 figures, to appear in Phys. Rev.

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

Search for lepton-flavor violation at HERA

A search for lepton-flavor-violating interactions $e p \to \mu X$ and $e p\to \tau X$ has been performed with the ZEUS detector using the entire HERA I data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data were taken at center-of-mass energies, $\sqrt{s}$, of 300 and 318 GeV. No evidence of lepton-flavor violation was found, and constraints were derived on leptoquarks (LQs) that could mediate such interactions. For LQ masses below $\sqrt{s}$, limits were set on $\lambda_{eq_1} \sqrt{\beta_{\ell q}}$, where $\lambda_{eq_1}$ is the coupling of the LQ to an electron and a first-generation quark $q_1$, and $\beta_{\ell q}$ is the branching ratio of the LQ to the final-state lepton $\ell$ ($\mu$ or $\tau$) and a quark $q$. For LQ masses much larger than $\sqrt{s}$, limits were set on the four-fermion interaction term $\lambda_{e q_\alpha} \lambda_{\ell q_\beta} / M_{\mathrm{LQ}}^2$ for LQs that couple to an electron and a quark $q_\alpha$ and to a lepton $\ell$ and a quark $q_\beta$, where $\alpha$ and $\beta$ are quark generation indices. Some of the limits are also applicable to lepton-flavor-violating processes mediated by squarks in $R$-Parity-violating supersymmetric models. In some cases, especially when a higher-generation quark is involved and for the process $e p\to \tau X$, the ZEUS limits are the most stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig. 6) adde

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

Multijet production in neutral current deep inelastic scattering at HERA and determination of alpha_s

Multijet production rates in neutral current deep inelastic scattering have been measured in the range of exchanged boson virtualities 10 < Q2 < 5000 GeV2. The data were taken at the ep collider HERA with centre-of-mass energy sqrt(s) = 318 GeV using the ZEUS detector and correspond to an integrated luminosity of 82.2 pb-1. Jets were identified in the Breit frame using the k_T cluster algorithm in the longitudinally invariant inclusive mode. Measurements of differential dijet and trijet cross sections are presented as functions of jet transverse energy E_{T,B}{jet}, pseudorapidity eta_{LAB}{jet} and Q2 with E_{T,B}{jet} > 5 GeV and -1 < eta_{LAB}{jet} < 2.5. Next-to-leading-order QCD calculations describe the data well. The value of the strong coupling constant alpha_s(M_Z), determined from the ratio of the trijet to dijet cross sections, is alpha_s(M_Z) = 0.1179 pm 0.0013(stat.) {+0.0028}_{-0.0046}(exp.) {+0.0064}_{-0.0046}(th.)Comment: 22 pages, 5 figure