208 research outputs found

    Design and Fabrication of Terahertz Metallic Gratings on a Two-Wire Waveguide

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    In this study, we present the design, fabrication and experimental characterization of waveguide-integrated gratings operating at THz frequencie

    Features of randomized electric-field assisted domain inversion in lithium tantalate

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    We report on bulk and guided-wave second-harmonic generation via random Quasi-Phase-Matching in Lithium Tantalate. By acquiring the far-field profiles at several wavelengths, we extract statistical information on the distribution of the quadratic nonlinearity as well as its average period, both at the surface and in the bulk of the sample. By investigating the distribution in the two regions we demonstrate a non-invasive approach to the study of poling dynamics

    Long-Term Frequency Stability of Laser Cavity Solitons

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    In this work, we show the long-term frequency stability of a laser cavity-solitons laser. When the laser is properly configured, it is possible to obtain robust soliton states, whose output was collected at the through output of the system to perform a long-term study. We have characterised the stability of the carrier comb line together with the repetition rate of the comb. These two frequency quantities fully determine the comb from a metrological perspective

    Stability of laser cavity-solitons for metrological applications

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    Laser cavity-solitons can appear in systems comprised of a nonlinear microcavity nested within an amplifying fiber loop. These states are robust and self-emergent and constitute an attractive class of solitons that are highly suitable for microcomb generation. Here, we present a detailed study of the free-running stability properties of the carrier frequency and repetition rate of single solitons, which are the most suitable states for developing robust ultrafast and high repetition rate comb sources. We achieve free-running fractional stability on both optical carrier and repetition rate (i.e., 48.9 GHz) frequencies on the order of 10^-9 for a 1 s gate time. The repetition rate results compare well with the performance of state-of-the-art (externally driven) microcomb sources, and the carrier frequency stability is in the range of performance typical of modern free-running fiber lasers. Finally, we show that these quantities can be controlled by modulating the laser pump current and the cavity length, providing a path for active locking and long-term stabilization

    Targeting the leukemic stem cell: the Holy Grail of leukemia therapy

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    Since the discovery of leukemic stem cells (LSCs) over a decade ago, many of their critical biological properties have been elucidated, including their distinct replicative properties, cell surface phenotypes, their increased resistance to chemo-therapeutic drugs and the involvement of growthpromoting chromosomal translocations. Of particular importance is their ability to transfer malignancy to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Furthermore, numerous studies demonstrate that acute myeloid leukemia arises from mutations at the level of stem cell, and chronic myeloid leukemia is also a stem cell disease. In this review, we will evaluate the main characteristics of LSCs elucidated in several well-documented leukemias. In addition, we will discuss points of therapeutic intervention. Promising therapeutic approaches include the targeting of key signal transduction pathways (for example, PI3K, Rac and Wnt) with smallmolecule inhibitors and specific cell surface molecules (for example, CD33, CD44 and CD123), with effective cytotoxic antibodies. Also, statins, which are already widely therapeutically used for a variety of diseases, show potential in targeting LSCs. In addition, drugs that inhibit ATP-binding cassette transporter proteins are being extensively studied, as they are important in drug resistance â a frequent characteristic of LSCs. Although the specific targeting of LSCs is a relatively new field, it is a highly promising battleground that may reveal the Holy Grail of cancer therapy. Originally published Leukemia, Vol. 23, No. 1, Jan 200

    Roles of the RAF/MEK/ERK Pathway in Cell Growth, Malignant Transformation and Drug Resistance

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    Growth factors and mitogens use the Ras/Raf/MEK/ERK signaling cascade to transmit signals from their receptors to regulate gene expression and prevent apoptosis. Some components of these pathways are mutated or aberrantly expressed in human cancer (e.g., Ras, B-Raf). Mutations also occur at genes encoding upstream receptors (e.g., EGFR and Flt-3) and chimeric chromosomal translocations (e.g., BCR-ABL) which transmit their signals through these cascades. Even in the absence of obvious genetic mutations, this pathway has been reported to be activated in over 50% of acute myelogenous leukemia and acute lymphocytic leukemia and is also frequently activated in other cancer types (e.g., breast and prostate cancers). Importantly, this increased expression is associated with a poor prognosis. The Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt pathways interact with each other to regulate growth and in some cases tumorigenesis. For example, in some cells, PTEN mutation may contribute to suppression of the Raf/MEK/ERK cascade due to the ability of activated Akt to phosphorylate and inactivate different Rafs. Although both of these pathways are commonly thought to have anti-apoptotic and drug resistance effects on cells, they display different cell lineage specific effects. For example, Raf/MEK/ERK is usually associated with proliferation and drug resistance of hematopoietic cells, while activation of the Raf/MEK/ERK cascade is suppressed in some prostate cancer cell lines which have mutations at PTEN and express high levels of activated Akt. Furthermore the Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt pathways also interact with the p53 pathway. Some of these interactions can result in controlling the activity and subcellular localization of Bim, Bak, Bax, Puma and Noxa. Raf/MEK/ERK may promote cell cycle arrest in prostate cells and this may be regulated by p53 as restoration of wild-type p53 in p53 deficient prostate cancer cells results in their enhanced sensitivity to chemotherapeutic drugs and increased expression of Raf/MEK/ERK pathway. Thus in advanced prostate cancer, it may be advantageous to induce Raf/MEK/ERK expression to promote cell cycle arrest, while in hematopoietic cancers it may be beneficial to inhibit Raf/MEK/ERK induced proliferation and drug resistance. Thus the Raf/MEK/ERK pathway has different effects on growth, prevention of apoptosis, cell cycle arrest and induction of drug resistance in cells of various lineages which may be due to the presence of functional p53 and PTEN and the expression of lineage specific factors. Originally published Biochim Biophys Acta, Vol. 1773, No. 8, August 200
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