205 research outputs found

    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

    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

    Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression

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    The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated.Methods and results: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibitor (TFPI) and the underlying mechanisms were determined. Further, arterial thrombosis by photochemical injury of the common carotid artery, and TF expression in the murine endothelium were examined in C57BL/6 mice treated with ticagrelor or clopidogrel. Ticagrelor, but not CAM, reduced TNF-α-induced TF expression via proteasomal degradation and TF activity, independently of the P2Y12 receptor and the equilibrative nucleoside transporter 1 (ENT1), an additional target of ticagrelor. In C57BL/6 mice, ticagrelor prolonged time to arterial occlusion, compared with clopidogrel, despite comparable antiplatelet effects. In line with our in vitro results, ticagrelor, but not clopidogrel, reduced TF expression in the endothelium of murine arteries.Conclusion: Ticagrelor, unlike clopidogrel, exhibits endothelial-specific antithrombotic properties and blunts arterial thrombus formation. The additional antithrombotic properties displayed by ticagrelor may explain its greater efficacy in reducing thrombotic events in clinical trials. These findings may provide the basis for new indications for ticagrelor

    Indoor free space optics link under the weak turbulence regime: measurements and model validation

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    This paper is a postprint of a paper submitted to and accepted for publication in [journal] and is subject to Institution of Engineering and Technology Copyright. The copy of record is available at IET Digital LibraryIn this study, the authors present the measurements performed on a free space optics (FSO) communications link using an indoor atmospheric chamber. In particular, the authors have generated several different optical turbulence conditions, demonstrating how even the weak turbulence regime can strongly affect the FSO link performance. The authors have carried out an in-depth analysis of the data collected during the measurements, and calculated the turbulence strength (i.e. scintillation index and Rytov variance) and the important performance metrics (i.e. the Q-factor and bit error rate) to evaluate the FSO link quality. Moreover, the authors have tested, for the first time, an appositely developed temporally-correlated gamma-gamma channel model to generate the temporal irradiance fluctuations observed at the receiver. This has been accomplished by using a complete analysis tool that enables the authors to fully simulate the experimental FSO link. Finally, the authors compare the generated time-series with the collected experimental data, showing a good agreement and thus proving the effectiveness of the model.This work was supported by the European Space Agency under grant no. 5401001020. We are very grateful to Dr. E. Armandillo for enlightening discussions. J. Perez's work was support by Spanish MINECO Juan de la Cierva Fellowship JCI-2012-14805. This research project falls within the frame of COST ICT Action IC1101 - Optical Wireless Communications - An Emerging Technology (OPTICWISE).Pernice, R.; Ando, A.; Cardinale, M.; Curcio, L.; Stivala, S.; Parisi, A.; Busacca, AC.... (2015). Indoor free space optics link under the weak turbulence regime: measurements and model validation. IET Communications. 9(1):62-70. https://doi.org/10.1049/iet-com.2014.0432S627091Tsukamoto, K., Hashimoto, A., Aburakawa, Y., & Matsumoto, M. (2009). The case for free space. IEEE Microwave Magazine, 10(5), 84-92. doi:10.1109/mmm.2009.933086Suriza, A. Z., Md Rafiqul, I., Wajdi, A. K., & Naji, A. W. (2013). Proposed parameters of specific rain attenuation prediction for Free Space Optics link operating in tropical region. Journal of Atmospheric and Solar-Terrestrial Physics, 94, 93-99. doi:10.1016/j.jastp.2012.11.008Nebuloni, R. (2005). Empirical relationships between extinction coefficient and visibility in fog. Applied Optics, 44(18), 3795. doi:10.1364/ao.44.003795García-Zambrana, A., Castillo-Vázquez, C., & Castillo-Vázquez, B. (2011). Outage performance of MIMO FSO links over strong turbulence and misalignment fading channels. Optics Express, 19(14), 13480. doi:10.1364/oe.19.013480Shokrollahi, A. (2006). Raptor codes. IEEE Transactions on Information Theory, 52(6), 2551-2567. doi:10.1109/tit.2006.874390MacKay, D. J. C. (2005). Fountain codes. IEE Proceedings - Communications, 152(6), 1062. doi:10.1049/ip-com:20050237Uysal, M., Jing Li, & Meng Yu. (2006). Error rate performance analysis of coded free-space optical links over gamma-gamma atmospheric turbulence channels. IEEE Transactions on Wireless Communications, 5(6), 1229-1233. doi:10.1109/twc.2006.1638639Tsiftsis, T. A. (2008). Performance of heterodyne wireless optical communication systems over gamma-gamma atmospheric turbulence channels. Electronics Letters, 44(5), 373. doi:10.1049/el:20083028Popoola, W. O., & Ghassemlooy, Z. (2009). BPSK Subcarrier Intensity Modulated Free-Space Optical Communications in Atmospheric Turbulence. Journal of Lightwave Technology, 27(8), 967-973. doi:10.1109/jlt.2008.2004950Nistazakis, H. E., Tsiftsis, T. A., & Tombras, G. S. (2009). Performance analysis of free-space optical communication systems over atmospheric turbulence channels. IET Communications, 3(8), 1402. doi:10.1049/iet-com.2008.0212Bayaki, E., Schober, R., & Mallik, R. (2009). Performance analysis of MIMO free-space optical systems in gamma-gamma fading. IEEE Transactions on Communications, 57(11), 3415-3424. doi:10.1109/tcomm.2009.11.080168Anguita, J. A., Neifeld, M. A., Hildner, B., & Vasic, B. (2010). Rateless Coding on Experimental Temporally Correlated FSO Channels. Journal of Lightwave Technology, 28(7), 990-1002. doi:10.1109/jlt.2010.2040136Andò, A., Mangione, S., Curcio, L., Stivala, S., Garbo, G., Pernice, R., & Busacca, A. C. (2013). Recovery Capabilities of Rateless Codes on Simulated Turbulent Terrestrial Free Space Optics Channel Model. International Journal of Antennas and Propagation, 2013, 1-8. doi:10.1155/2013/692915Ghassemlooy, Z., Le Minh, H., Rajbhandari, S., Perez, J., & Ijaz, M. (2012). Performance Analysis of Ethernet/Fast-Ethernet Free Space Optical Communications in a Controlled Weak Turbulence Condition. Journal of Lightwave Technology, 30(13), 2188-2194. doi:10.1109/jlt.2012.2194271Xiaoming Zhu, & Kahn, J. M. (2002). Free-space optical communication through atmospheric turbulence channels. IEEE Transactions on Communications, 50(8), 1293-1300. doi:10.1109/tcomm.2002.800829Xu, F., Khalighi, A., Caussé, P., & Bourennane, S. (2009). Channel coding and time-diversity for optical wireless links. Optics Express, 17(2), 872. doi:10.1364/oe.17.00087

    Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activity

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    It is well known that natural products are a rich source of compounds for applications in medicine, pharmacy, and biology. However, the exact molecular mechanisms of natural agents in human health have not been clearly defined. Here, we demonstrate for the first time that the polyphenolic phytoalexin resveratrol promotes expression and activity of Argonaute2 (Ago2), a central RNA interference (RNAi) component, which thereby inhibits breast cancer stem-like cell characteristics by increasing the expression of a number of tumour-suppressive miRNAs, including miR-16, -141, -143, and -200c. Most importantly, resveratrol-induced Ago2 resulted in a long-term gene silencing response. We also found that pterostilbene, which is a natural dimethylated resveratrol analogue, is capable of mediating Ago2-dependent anti-cancer activity in a manner mechanistically similar to that of resveratrol. These findings suggest that the dietary intake of natural products contributes to the prevention and treatment of diseases by regulating the RNAi pathway

    Hypervalent iodine reagents in the total synthesis of natural products

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    P21-PARP-1 pathway is involved in cigarette smoke-induced lung DNA damage and cellular senescence

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    Persistent DNA damage triggers cellular senescence, which may play an important role in the pathogenesis of cigarette smoke (CS)-induced lung diseases. Both p21(CDKN1A) (p21) and poly(ADP-ribose) polymerase-1 (PARP-1) are involved in DNA damage and repair. However, the role of p21-PARP-1 axis in regulating CS-induced lung DNA damage and cellular senescence remains unknown. We hypothesized that CS causes DNA damage and cellular senescence through a p21-PARP-1 axis. To test this hypothesis, we determined the levels of γH2AX (a marker for DNA double-strand breaks) as well as non-homologous end joining proteins (Ku70 and Ku80) in lungs of mice exposed to CS. We found that the level of γH2AX was increased, whereas the level of Ku70 was reduced in lungs of CS-exposed mice. Furthermore, p21 deletion reduced the level of γH2AX, but augmented the levels of Ku70, Ku80, and PAR in lungs by CS. Administration of PARP-1 inhibitor 3-aminobenzamide increased CS-induced DNA damage, but lowered the levels of Ku70 and Ku80, in lungs of p21 knockout mice. Moreover, 3-aminobenzamide increased senescence-associated β-galactosidase activity, but decreased the expression of proliferating cell nuclear antigen in mouse lungs in response to CS. Interestingly, 3-aminobenzamide treatment had no effect on neutrophil influx into bronchoalveolar lavage fluid by CS. These results demonstrate that the p21-PARP-1 pathway is involved in CS-induced DNA damage and cellular senescence

    Ceremonial plant consumption at Middle Bronze Age Büklükale, Kırıkkale Province, central Turkey

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    A shaft-like room at the Middle Bronze Age site of Büklükale in central Turkey preserved a rich archaeobotanical assemblage of charred and mineralised plant remains, dominated by fruits, spices and nuts mixed with probable bread and wood charcoals. The remains were recovered in association with numerous ceramic vessels, jewellery and exotic artefacts. We combine identification and analysis of the seeds and wood charcoals contained in this deposit with studies of Old Assyrian and Hittite textual records to investigate the circumstances of the assemblage’s formation and its significance for further understanding trade and plant consumption in Bronze Age Anatolia. We present the earliest archaeobotanical example in the region of rare and exotic plant species being consumed in the context of one or more social gatherings, including those possibly linked to ceremonial or ritual events. This offers new insights into the role of plants in the economic and social life of the southwest Asian Bronze Age, as well as the role of commensality and feasting in early states
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