Dynamical back-action at 5.5 GHz in a corrugated optomechanical beam

[EN] We report on the optomechanical properties of a breathing mechanical mode oscillating at 5.5 GHz in a 1D corrugated Si nanobeam. This mode has an experimental single-particle optomechanical coupling rate of vertical bar g(o, OM)vertical bar= 1.8 MHz (vertical bar g(o, OM)vertical bar/2 pi=0.3 MHz) and shows strong dynamical back-action effects at room temperature. The geometrical flexibility of the unit-cell would lend itself to further engineering of the cavity region to localize the mode within the full phononic band-gap present at 4 GHz while keeping high go, OM values. This would lead to longer lifetimes at cryogenic temperatures, due to the suppression of acoustic leakage.This work was supported by the EU through the FP7 project TAILPHOX (ICT-FP7-233883) and the ERC Advanced Grant SOULMAN (ERC-FP7-321122) and the Spanish projects TAPHOR (MAT2012-31392). D.N-U and J.G-B acknowledge support in the form of postdoctoral fellowships from the Catalan (Beatriu de Pinos) and the Spanish (Juan de la Cierva) governments, respectively.Navarro-Urrios, D.; Gomis-Bresco, J.; El-Jallal, S.; Oudich, M.; Pitanti, A.; Capuj, N.; Tredicucci, A.... (2014). Dynamical back-action at 5.5 GHz in a corrugated optomechanical beam. AIP Advances. 4(12). https://doi.org/10.1063/1.4902171S412Aspelmeyer, M., Kippenberg, T. J., & Marquardt, F. (Eds.). (2014). Cavity Optomechanics. doi:10.1007/978-3-642-55312-7Kippenberg, T. J., Rokhsari, H., Carmon, T., Scherer, A., & Vahala, K. J. (2005). Analysis of Radiation-Pressure Induced Mechanical Oscillation of an Optical Microcavity. Physical Review Letters, 95(3). doi:10.1103/physrevlett.95.033901Hossein-Zadeh, M., Rokhsari, H., Hajimiri, A., & Vahala, K. J. (2006). Characterization of a radiation-pressure-driven micromechanical oscillator. Physical Review A, 74(2). doi:10.1103/physreva.74.023813Eichenfield, M., Chan, J., Camacho, R. M., Vahala, K. J., & Painter, O. (2009). Optomechanical crystals. Nature, 462(7269), 78-82. doi:10.1038/nature08524Pennec, Y., Laude, V., Papanikolaou, N., Djafari-Rouhani, B., Oudich, M., El Jallal, S., … Martínez, A. (2014). Modeling light-sound interaction in nanoscale cavities and waveguides. Nanophotonics, 3(6). doi:10.1515/nanoph-2014-0004Chan, J., Alegre, T. P. M., Safavi-Naeini, A. H., Hill, J. T., Krause, A., Gröblacher, S., … Painter, O. (2011). Laser cooling of a nanomechanical oscillator into its quantum ground state. Nature, 478(7367), 89-92. doi:10.1038/nature10461Safavi-Naeini, A. H., Alegre, T. P. M., Chan, J., Eichenfield, M., Winger, M., Lin, Q., … Painter, O. (2011). Electromagnetically induced transparency and slow light with optomechanics. Nature, 472(7341), 69-73. doi:10.1038/nature09933Pennec, Y., Rouhani, B. D., Li, C., Escalante, J. M., Martinez, A., Benchabane, S., … Papanikolaou, N. (2011). Band gaps and cavity modes in dual phononic and photonic strip waveguides. AIP Advances, 1(4), 041901. doi:10.1063/1.3675799Gomis-Bresco, J., Navarro-Urrios, D., Oudich, M., El-Jallal, S., Griol, A., Puerto, D., … Torres, C. M. S. (2014). A one-dimensional optomechanical crystal with a complete phononic band gap. Nature Communications, 5(1). doi:10.1038/ncomms5452Oudich, M., El-Jallal, S., Pennec, Y., Djafari-Rouhani, B., Gomis-Bresco, J., Navarro-Urrios, D., … Makhoute, A. (2014). Optomechanic interaction in a corrugated phoxonic nanobeam cavity. Physical Review B, 89(24). doi:10.1103/physrevb.89.245122Chan, J., Safavi-Naeini, A. H., Hill, J. T., Meenehan, S., & Painter, O. (2012). Optimized optomechanical crystal cavity with acoustic radiation shield. Applied Physics Letters, 101(8), 081115. doi:10.1063/1.4747726Safavi-Naeini, A. H., Hill, J. T., Meenehan, S., Chan, J., Gröblacher, S., & Painter, O. (2014). Two-Dimensional Phononic-Photonic Band Gap Optomechanical Crystal Cavity. Physical Review Letters, 112(15). doi:10.1103/physrevlett.112.153603Johnson, S. G., Ibanescu, M., Skorobogatiy, M. A., Weisberg, O., Joannopoulos, J. D., & Fink, Y. (2002). Perturbation theory for Maxwell’s equations with shifting material boundaries. Physical Review E, 65(6). doi:10.1103/physreve.65.066611Navarro-Urrios, D., Gomis-Bresco, J., Capuj, N. E., Alzina, F., Griol, A., Puerto, D., … Sotomayor-Torres, C. M. (2014). Optical and mechanical mode tuning in an optomechanical crystal with light-induced thermal effects. Journal of Applied Physics, 116(9), 093506. doi:10.1063/1.4894623Barclay, P. E., Srinivasan, K., & Painter, O. (2005). Nonlinear response of silicon photonic crystal micresonators excited via an integrated waveguide and fiber taper. Optics Express, 13(3), 801. doi:10.1364/opex.13.000801J. Chan, Ph.D. thesis, California Institute of Technology, Los Angeles, 2014.Gorodetsky, M. L., Schliesser, A., Anetsberger, G., Deleglise, S., & Kippenberg, T. J. (2010). Determination of the vacuum optomechanical coupling rate using frequency noise calibration. Optics Express, 18(22), 23236. doi:10.1364/oe.18.02323

Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells

INTRODUCTION: We have shown previously that overexpression of constitutively active Akt or activation of Akt caused by constitutively active Ras or human epidermal growth factor receptor-2 (HER2) confers on breast cancer cells resistance to chemotherapy or radiotherapy. As an expanded study we here report differential responses in terms of phosphorylation and activation of Akt as a result of treatment with doxorubicin in a panel of breast cancer cell lines. METHODS: The levels of Akt phosphorylation and activity were measured by Western blot analysis with an anti-Ser473-phosphorylated Akt antibody and by in vitro Akt kinase assay using glycogen synthase kinase-3 as a substrate. RESULTS: Within 24 hours after exposure to doxorubicin, MCF7, MDA468 and T47D cells showed a drug-dose-dependent increase in the levels of phosphorylated Akt; in contrast, SKBR3 and MDA231 cells showed a decrease in the levels of phosphorylated Akt, and minimal or no changes were detected in MDA361, MDA157 and BT474 cells. The doxorubicin-induced Akt phosphorylation was correlated with increased kinase activity and was dependent on phosphoinositide 3-kinase (PI3-K). An increased baseline level of Akt was also found in MCF7 cells treated with ionizing radiation. The cellular responses to doxorubicin-induced Akt phosphorylation were potentiated after the expression of Akt upstream activators including HER2, HER3 and focal adhesion kinase. CONCLUSION: Taken together with our recent published results showing that constitutive Akt mediates resistance to chemotherapy or radiotherapy, our present data suggest that the doxorubicin-induced phosphorylation and activation of Akt might reflect a cellular defensive mechanism of cancer cells to overcome doxorubicin-induced cytotoxic effects, which further supports the current efforts of targeting PI3-K/Akt for enhancing the therapeutic responses of breast cancer cells to chemotherapy and radiotherapy

Altered Expression of Insulin Receptor Isoforms in Breast Cancer

PURPOSE: Insulin-like growth factor (IGF) signaling through human insulin receptor isoform A (IR-A) contributes to tumorigenesis and intrinsic resistance to anti-IGF1R therapy. In the present study, we (a) developed quantitative TaqMan real time-PCR-based assays (qRT-PCR) to measure human insulin receptor isoforms with high specificity, (b) evaluated isoform expression levels in molecularly-defined breast cancer subtypes, and (c) identified the IR-A:IR-B mRNA ratio as a potential biomarker guiding patient stratification for anti-IGF therapies. EXPERIMENTAL DESIGN: mRNA expression levels of IR-A and IR-B were measured in 42 primary breast cancers and 19 matched adjacent normal tissues with TaqMan qRT-PCR assays. The results were further confirmed in 165 breast cancers. The tumor samples were profiled using whole genome microarrays and subsequently subtyped using the PAM50 breast cancer gene signature. The relationship between the IR-A:IR-B ratio and cancer subtype, as well as markers of proliferation were characterized. RESULTS: The mRNA expression levels of IR-A in the breast tumors were similar to those observed in the adjacent normal tissues, while the mRNA levels of IR-B were significantly decreased in tumors. The IR-A:IR-B ratio was significantly higher in luminal B breast cancer than in luminal A. Strong concordance between the IR-A:IR-B ratio and the composite Oncotype DX proliferation score was observed for stratifying the latter two breast cancer subtypes. CONCLUSIONS: The reduction in IR-B expression is the key to the altered IR-A:IR-B ratio observed in breast cancer. The IR-A:IR-B ratio may have biomarker utility in guiding a patient stratification strategy for an anti-IGF therapeutic

Cyclophilin C-associated protein (CyCAP) knock-out mice spontaneously develop colonic mucosal hyperplasia and exaggerated tumorigenesis after treatment with carcinogen azoxymethane1

<p>Abstract</p> <p>Background</p> <p>The discovery of a "serrated neoplasia pathway" has highlighted the role of hyperplastic lesions of the colon as the significant precursor of colorectal adenocarcinoma. In mice, hyperplasia of the colonic mucosa is a regular phenomenon after a challenge with colonic carcinogens indicating that mucosal hyperproliferation and thickening, even without cytological dysplasia, represents an early pre-malignant change. Cyclophilin C-associated protein (CyCAP) has been described to down-modulate endotoxin signaling in colorectal murine mucosa and is a murine orthologue of the tumor-associated antigen 90 K (TAA90K)/mac-2-binding protein.</p> <p>Methods</p> <p>Female Balb/c wild-type (WT) and CyCAP knock-out (KO) mice (6–8 weeks old) were administered 2 or 6 weekly subcutaneous injections of azoxymethane. The animals were evaluated post-injection at six weeks for aberrant crypt foci (ACF) study and at five months for colon tumor measurement. The thickness of the colon crypts was measured in microns and the number of colonocytes per crypt was also determined in well-oriented crypts. Morphometric analyses of the colon mucosa were also performed in untreated 6–8 weeks old KO and WT animals. Formalin-fixed/paraffin-embedded colon sections were also studied by immunohistochemistry to determine the Ki-67 proliferation fraction of the colon mucosa, β-catenin cellular localization, cyclin D1, c-myc, and lysozyme in Paneth cells.</p> <p>Results</p> <p>Cyclophilin C-associated protein (CyCAP)^-/-mice, spontaneously developed colonic mucosal hyperplasia early in life compared to wild-type mice (WT) (p < 0.0001, T-test) and crypts of colonic mucosa of the (CyCAP)^-/-mice show higher proliferation rate (p = 0.039, Mann-Whitney Test) and larger number of cyclin D1-positive cells (p < 0.0001, Mann-Whitney Test). Proliferation fraction and cyclin D1 expression showed positive linear association (p = 0.019, Linear-by-Linear Association). The hyperplasia was even more pronounced in CyCAP^-/-mice than in WT after challenge with azoxymethane (p = 0.005, T-test). The length of the crypts (r = 0.723, p = 0.018, Spearman Correlation) and the number of colonocytes per crypt (r = 0.863, p = 0.001, Spearman Correlation) in non-tumorous areas were positively associated with azoxymethane-induced number of tumors. CyCAP^-/-developed larger numbers of tumors than WT animals (p = 0.003, T-Test) as well as overall larger tumor mass (p = 0.016, T-Test). Membranous β-catenin was focally overexpressed in KO mice including proliferative zone of the crypts.</p> <p>Conclusion</p> <p>CyCAP^-/-represent the first described model of spontaneous colonic mucosal hyperplasia. We conclude that CyCAP-deficient mice spontaneously and after challenge with carcinogen develop significantly more colorectal mucosal hyperplasia, an early stage in murine colonic carcinogenesis.</p

SREB, a GATA Transcription Factor That Directs Disparate Fates in Blastomyces dermatitidis Including Morphogenesis and Siderophore Biosynthesis

Blastomyces dermatitidis belongs to a group of human pathogenic fungi that exhibit thermal dimorphism. At 22°C, these fungi grow as mold that produce conidia or infectious particles, whereas at 37°C they convert to budding yeast. The ability to switch between these forms is essential for virulence in mammals and may enable these organisms to survive in the soil. To identify genes that regulate this phase transition, we used Agrobacterium tumefaciens to mutagenize B. dermatitidis conidia and screened transformants for defects in morphogenesis. We found that the GATA transcription factor SREB governs multiple fates in B. dermatitidis: phase transition from yeast to mold, cell growth at 22°C, and biosynthesis of siderophores under iron-replete conditions. Insertional and null mutants fail to convert to mold, do not accumulate significant biomass at 22°C, and are unable to suppress siderophore biosynthesis under iron-replete conditions. The defect in morphogenesis in the SREB mutant was independent of exogenous iron concentration, suggesting that SREB promotes the phase transition by altering the expression of genes that are unrelated to siderophore biosynthesis. Using bioinformatic and gene expression analyses, we identified candidate genes with upstream GATA sites whose expression is altered in the null mutant that may be direct or indirect targets of SREB and promote the phase transition. We conclude that SREB functions as a transcription factor that promotes morphogenesis and regulates siderophore biosynthesis. To our knowledge, this is the first gene identified that promotes the conversion from yeast to mold in the dimorphic fungi, and may shed light on environmental persistence of these pathogens

EGFR-Mediated Carcinoma Cell Metastasis Mediated by Integrin αvβ5 Depends on Activation of c-Src and Cleavage of MUC1

Receptor tyrosine kinases and integrins play an essential role in tumor cell invasion and metastasis. We previously showed that EGF and other growth factors induce human carcinoma cell invasion and metastasis mediated by integrin αvβ5 that is prevented by Src blockade [1]. MUC1, a transmembrane glycoprotein, is expressed in most epithelial tumors as a heterodimer consisting of an extracellular and a transmembrane subunit. The MUC1 cytoplasmic domain of the transmembrane subunit (MUC1.CD) translocates to the nucleus where it promotes the transcription of a metastatic gene signature associated with epithelial to mesenchymal transition. Here, we demonstrate a requirement for MUC1 in carcinoma cell metastasis dependent on EGFR and Src without affecting primary tumor growth. EGF stimulates Src-dependent MUC1 cleavage and nuclear localization leading to the expression of genes linked to metastasis. Moreover, expression of MUC1.CD results in its nuclear localization and is sufficient for transcription of the metastatic gene signature and tumor cell metastasis. These results demonstrate that EGFR and Src activity contribute to carcinoma cell invasion and metastasis mediated by integrin αvβ5 in part by promoting proteolytic cleavage of MUC1 and highlight the ability of MUC1.CD to promote metastasis in a context-dependent manner. Our findings may have implications for the use and future design of targeted therapies in cancers known to express EGFR, Src, or MUC1

Protein tyrosine phosphatases expression during development of mouse superior colliculus

Protein tyrosine phosphatases (PTPs) are key regulators of different processes during development of the central nervous system. However, expression patterns and potential roles of PTPs in the developing superior colliculus remain poorly investigated. In this study, a degenerate primer-based reverse transcription-polymerase chain reaction (RT-PCR) approach was used to isolate seven different intracellular PTPs and nine different receptor-type PTPs (RPTPs) from embryonic E15 mouse superior colliculus. Subsequently, the expression patterns of 11 PTPs (TC-PTP, PTP1C, PTP1D, PTP-MEG2, PTP-PEST, RPTPJ, RPTPε, RPTPRR, RPTPσ, RPTPκ and RPTPγ) were further analyzed in detail in superior colliculus from embryonic E13 to postnatal P20 stages by quantitative real-time RT-PCR, Western blotting and immunohistochemistry. Each of the 11 PTPs exhibits distinct spatiotemporal regulation of mRNAs and proteins in the developing superior colliculus suggesting their versatile roles in genesis of neuronal and glial cells and retinocollicular topographic mapping. At E13, additional double-immunohistochemical analysis revealed the expression of PTPs in collicular nestin-positive neural progenitor cells and RC-2-immunoreactive radial glia cells, indicating the potential functional importance of PTPs in neurogenesis and gliogenesis

Regulation a court terme des recepteurs gonadotropes par la LH et l'hCG.

National audienc

Regulation a court terme des recepteurs gonadotropes par la LH et l'hCG.

National audienc