3,443 research outputs found

    Macro aerodynamic devices controlled by micro systems

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    Micro-ElectroMechanical-Systems (MEMS) have emerged as a major enabling technology across the engineering disciplines. In this study, the possibility of applying MEMS to the aerodynamic field was explored. We have demonstrated that microtransducers can be used to control the motion of a delta wing in a wind tunnel and can even maneuver a scaled aircraft in flight tests. The main advantage of using micro actuators to replace the traditional control surface is the significant reduction of radar cross-sections. At a high angle of attack, a large portion of the suction loading on a delta wing is contributed by the leading edge separation vortices which originate from thin boundary layers at the leading edge. We used microactuators with a thickness comparable to that of the boundary layer in order to alter the separation process and thus achieved control of the global motion by minute perturbations

    Superior Antitumor Activity of a Novel Bispecific Antibody Cotargeting Human Epidermal Growth Factor Receptor 2 and Type I Insulin-like Growth Factor Receptor

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    The humanized anti-HER2 monoclonal antibody (mAb) trastuzumab (Herceptin; Genentech) effectively inhibits human epidermal growth factor receptor 2 (HER2)-positive breast tumors. However, many patients responding to treatment often develop resistance. Cross-talk between type I insulin-like growth factor receptor (IGF-IR) and HER2 and elevated IGF-IR signaling have been implicated in tumor cell resistance to trastuzumab therapy. Previously, we reported that the anti-IGF-IR mAb m590 inhibits proliferation and migration of breast cancer MCF-7 cells in vitro. Here, we generated a 'knobs-into-holes' bispecific antibody (Bi-Ab) against HER2 and IGF-IR by engineering trastuzumab and m590. We compared the effects of Bi-Ab treatment in vitro and in SKOV-3 HER2- and IGF-IR-overexpressing cancer xenograft mouse model with those of m590 and trastuzumab treatment alone or in combination. Bi-Ab effectively inhibited proliferation of HER2- and IGF-IR-overexpressing ovarian cancer SKOV-3 cells in vitro by ablating receptor phosphorylation and downstream PI3K/Akt and mitogen-activated protein kinase signaling. Bi-Ab more effectively inhibited cancer growth in SKOV-3 HER2- and IGF-IR-overexpressing cancer xenograft mouse model than m590 and trastuzumab alone or in combination. Mice bearing SKOV-3 HER2- and IGF-IR-overexpressing xenografts showed extensive and sustainable tumor regression when treated with Bi-Ab. Our results suggest that Bi-Ab has superior antitumor activity compared with monospecific antibodies, and cotargeting HER2 and IGF-IR may be clinically beneficial in minimizing the acquired resistance to trastuzumab therapy. Mol Cancer Ther; 13(1); 90-100. (c)2013 AACR.postprin

    Hepatoprotective effects of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced acute liver hepatotoxicity in rats

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    Aim of the study: Coptidis rhizoma (CR, Chinese name is Huanglian) has been used in treating infectious and inflammatory diseases for two thousand years in Traditional Chinese Medicine (TCM). Its related pharmacological basis for the therapeutics has been studied intensively, but CR can also be used for vomiting of "dampness-heat type or acid regurgitation" due to "liver-fire attacking stomach" in TCM, whose symptoms seem to link the hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. To clarify this ethnopharmacological relevance, hepatoprotective effect of Coptidis rhizoma aqueous extract (CRAE) and its possible mechanism were studied in rats intoxicated with carbon tetrachloride (CCl 4) in the present study. Materials and methods: Sprague-Dawley (SD) rats aged 7 weeks old were intraperitoneally injected with CCl 4 at a dose of 1.0 ml/kg as a 50% olive oil solution. The rats were orally given the CRAE at doses of 400, 600, 800 mg/kg and 120 mg/kg berberine body weight (BW) after 6 h of CCl 4 treatment. At 24 h after CCl 4 injection, samples of blood and liver were collected and then biochemical parameters and histological studies were carried out. Results: The results showed that CRAE and berberine inhibited significantly the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and increased the activity of superoxide dismutase (SOD). Observation on the hepatoprotective effect of berberine was consistent to that of CRAE. Conclusion: The study is the first time to demonstrate that CRAE has hepatoprotective effect on acute liver injuries induced by CCl 4, and the results suggest that the effect of CRAE against CCl 4-induced liver damage is related to antioxidant property. © 2009 Elsevier Ireland Ltd. All rights reserved.postprin

    Energetics and atomic mechanisms of dislocation nucleation in strained epitaxial layers

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    We study numerically the energetics and atomic mechanisms of misfit dislocation nucleation and stress relaxation in a two-dimensional atomistic model of strained epitaxial layers on a substrate with lattice misfit. Relaxation processes from coherent to incoherent states for different transition paths are studied using interatomic potentials of Lennard-Jones type and a systematic saddle point and transition path search method. The method is based on a combination of repulsive potential minimization and the Nudged Elastic Band method. For a final state with a single misfit dislocation, the minimum energy path and the corresponding activation barrier are obtained for different misfits and interatomic potentials. We find that the energy barrier decreases strongly with misfit. In contrast to continuous elastic theory, a strong tensile-compressive asymmetry is observed. This asymmetry can be understood as manifestation of asymmetry between repulsive and attractive branches of pair potential and it is found to depend sensitively on the form of the potential.Comment: 11 pages, 9 figures, to appear in Phys. Rev.

    Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.

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    Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.published_or_final_versio

    Modelling Pricing Policy Based on Shelf-Life of Non Homogeneous Available-To-Promise in Fruit Supply Chains

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    [EN] Fruit Supply Chains (SCs) are influenced by uncontrollable natural factors causing heterogeneity in their products, as regards certain attributes that are relevant to customers and vary over time because of the shelf-life. As a consequence customers should be served not only with the required quantity and due date as usual, but also with the quality, freshness and homogeneity specified in their orders. The order promising process (OPP) is based on the uncommitted availability of homogeneous product quantities in planned lots (ATP) that are uncertain. Therefore, there is a risk of not being reliable in the commitments because of discrepancies between the real and planned homogeneous quantities. Furthermore, due to the shelf-life (SL), serving customers with the freshest product introduce the risk of increasing waste because of the aging process. To efficiently manage these risks, this work proposes a mathematical model for handling the heterogeneous ATP in fruit SCs and a pricing policy based on the product SL in the moment of delivery. In order to illustrate the application of the modelling approach, a short numerical example is introduced. The example evidences a conflictive situation when optimizing the assignation of homogeneous ATP between serving orders with fresh and more valuable product, what could lead to increase the risk of having waste because of expiration, and consequently, more costs and less profit.This research has been supported by the Ministry of Science, Technology and Telecommunications, government of Costa Rica (MICITT), through the program of innovation and human capital for competitiveness (PINN) (PED-019-2015-1).Grillo-Espinoza, H.; Alemany Díaz, MDM.; Ortiz Bas, Á. (2016). Modelling Pricing Policy Based on Shelf-Life of Non Homogeneous Available-To-Promise in Fruit Supply Chains. IFIP Advances in Information and Communication Technology. 480:608-617. https://doi.org/10.1007/978-3-319-45390-3_52S608617480Alarcon, F., Alemany, M.M.E., Lario, F.C., Oltra, R.F.: The lack of homogeneity in the product (LHP) in the ceramic tile industry and its impact on the reallocation of inventories. Boletin Soc. Espanola Ceram. Vidr. 50, 49–57 (2011). doi: 10.3989/cyv.072011Alemany, M.M.E., Grillo, H., Ortiz, A., Fuertes-Miquel, V.S.: A fuzzy model for shortage planning under uncertainty due to lack of homogeneity in planned production lots. Appl. Math. Model. (2015). doi: 10.1016/j.apm.2014.12.057Alemany, M.M.E., Lario, F.-C., Ortiz, A., Gomez, F.: Available-To-Promise modeling for multi-plant manufacturing characterized by lack of homogeneity in the product: an illustration of a ceramic case. Appl. Math. Model. 37, 3380–3398 (2013). doi: 10.1016/j.apm.2012.07.022Blanco, A.M., Masini, G., Petracci, N., Bandoni, J.A.: Operations management of a packaging plant in the fruit industry. J. Food Eng. 70, 299–307 (2005). doi: 10.1016/j.jfoodeng.2004.05.075Grillo, H., Alemany, M.M.E., Ortiz, A.: A review of mathematical models for supporting the order promising process under Lack of Homogeneity in Product and other sources of uncertainty. Comput. Ind. Eng. 91, 239–261 (2016)Kilic, O.A., van Donk, D.P., Wijngaard, J., Tarim, S.A.: Order acceptance in food processing systems with random raw material requirements. Spectrum 32, 905–925 (2010). doi: 10.1007/s00291-010-0213-4Lin, J.T., Hong, I.H., Wu, C.H., Wang, K.S.: A model for batch available-to-promise in order fulfillment processes for TFT-LCD production chains. Comput. Ind. Eng. 59, 720–729 (2010). doi: 10.1016/j.cie.2010.07.026Maihami, R., Karimi, B.: Optimizing the pricing and replenishment policy for non-instantaneous deteriorating items with stochastic demand and promotional efforts. Comput. Oper. Res. 51, 302–312 (2014). doi: 10.1016/j.cor.2014.05.022Mundi, M.I., Alemany, M.M.E., Poler, R., Fuertes-Miquel, V.S.: Fuzzy sets to model master production effectively in Make to Stock companies with Lack of Homogeneity in the Product. Fuzzy Sets Syst. 293, 95–112 (2016). http://dx.doi.org/10.1016/j.fss.2015.06.009Tsao, Y.-C., Sheen, G.-J.: Dynamic pricing, promotion and replenishment policies for a deteriorating item under permissible delay in payments. Part Spec. Issue Top. Real-Time Supply Chain Manag. 35, 3562–3580 (2008). doi: 10.1016/j.cor.2007.01.02

    Decreased MCM2-6 in Drosophila S2 cells does not generate significant DNA damage or cause a marked increase in sensitivity to replication interference.

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    A reduction in the level of some MCM proteins in human cancer cells (MCM5 in U20S cells or MCM3 in Hela cells) causes a rapid increase in the level of DNA damage under normal conditions of cell proliferation and a loss of viability when the cells are subjected to replication interference. Here we show that Drosophila S2 cells do not appear to show the same degree of sensitivity to MCM2-6 reduction. Under normal cell growth conditions a reduction of >95% in the levels of MCM3, 5, and 6 causes no significant short term alteration in the parameters of DNA replication or increase in DNA damage. MCM depleted cells challenged with HU do show a decrease in the density of replication forks compared to cells with normal levels of MCM proteins, but this produces no consistent change in the levels of DNA damage observed. In contrast a comparable reduction of MCM7 levels has marked effects on viability, replication parameters and DNA damage in the absence of HU treatment

    Teaching lean construction: perspectives on theory and practice

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    This paper builds on the IGLC paper, “Different Perspectives on Teaching Lean Construction,” presented last year by Tsao et al. that documented teaching approaches from three different Lean Construction (LC) university course offerings. It aggregated the approaches taken by the course offerings, the Lean Construction Institute (LCI), and the Associated General Contractors of America to develop recommendations for learning modules, outcomes, and strategies for an introductory LC university course. This paper provides four additional distinct perspectives to continue the conversation about teaching LC in a university setting. It illustrates the authors’ differences in teaching approaches, experiences, and lessons learned from course offerings in the United States and Lebanon. The paper offers additional ideas for providing “proof of concept” to students and further illustrates how teaching LC effectively requires a combination of readings, lectures, discussions, simulation exercises, field trips, and guest speakers to mix theory with action. The paper then aggregates seven teaching perspectives in a single table to provide an overview of different approaches for teaching an introductory university-level course on LC

    How metal films de-wet substrates - identifying the kinetic pathways and energetic driving forces

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    We study how single-crystal chromium films of uniform thickness on W(110) substrates are converted to arrays of three-dimensional (3D) Cr islands during annealing. We use low-energy electron microscopy (LEEM) to directly observe a kinetic pathway that produces trenches that expose the wetting layer. Adjacent film steps move simultaneously uphill and downhill relative to the staircase of atomic steps on the substrate. This step motion thickens the film regions where steps advance. Where film steps retract, the film thins, eventually exposing the stable wetting layer. Since our analysis shows that thick Cr films have a lattice constant close to bulk Cr, we propose that surface and interface stress provide a possible driving force for the observed morphological instability. Atomistic simulations and analytic elastic models show that surface and interface stress can cause a dependence of film energy on thickness that leads to an instability to simultaneous thinning and thickening. We observe that de-wetting is also initiated at bunches of substrate steps in two other systems, Ag/W(110) and Ag/Ru(0001). We additionally describe how Cr films are converted into patterns of unidirectional stripes as the trenches that expose the wetting layer lengthen along the W[001] direction. Finally, we observe how 3D Cr islands form directly during film growth at elevated temperature. The Cr mesas (wedges) form as Cr film steps advance down the staircase of substrate steps, another example of the critical role that substrate steps play in 3D island formation
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