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1

Chiesa, Enrica, Silvia Pisani, Barbara Colzani, Rossella Dorati, Bice Conti, Tiziana Modena, Kevin Braekmans et Ida Genta. « Intra-Articular Formulation of GE11-PLGA Conjugate-Based NPs for Dexamethasone Selective Targeting—In Vitro Evaluation ». International Journal of Molecular Sciences 19, no 8 (6 août 2018) : 2304. http://dx.doi.org/10.3390/ijms19082304.

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Selectively targeted nanoscale drug delivery systems have recently emerged as promising intravenously therapeutic option for most chronic joint diseases. Here, a newly synthetized dodecapeptide (GE11)-polylactide-co-glycolide (PLGA)-based conjugate was used to prepare smart nanoparticles (NPs) intended for intra-articular administration and for selectively targeting Epidermal Growth Factor Receptor (EGFR). GE11-PLGA conjugate-based NPs are specifically uptaken by EGFR-overexpressed fibroblast; such as synoviocytes; which are the primarily cellular component involved in the development of destructive joint inflammation. The selective uptake could help to tune drug effectiveness in joints and to decrease local and systemic side effects. Dexamethasone (DXM) is a glucorticoid drug commonly used in joint disease treatment for both systemic and local administration route. In the present research; DXM was efficiently loaded into GE11-PLGA conjugate-based NPs through an eco-friendly nanoprecipitation method set up for this purpose. DXM loaded GE11-PLGA conjugate-based NPs revealed satisfactory ex vivo cytocompatibility; with proper size (≤150 nm) and good dimensional stability in synovial fluid. Intra-articular formulation was developed embedding DXM loaded GE11-PLGA conjugate-based NPs into thermosetting chitosan-based hydrogel; forming a biocompatible composite hydrogel able to quickly turn from liquid state into gel state at physiological temperature; within 15 min. Moreover; the use of thermosetting chitosan-based hydrogel extends the local release of active agent; DXM.
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Huang, Xueqin, Lingzhi Chen, Yuping Zhang, Suyan Zhou, Huai-Hong Cai, Ting Li, Hua Jin, Jiye Cai, Haibo Zhou et Jiang Pi. « GE11 Peptide Conjugated Liposomes for EGFR-Targeted and Chemophotothermal Combined Anticancer Therapy ». Bioinorganic Chemistry and Applications 2021 (31 mars 2021) : 1–15. http://dx.doi.org/10.1155/2021/5534870.

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How to actively target tumor sites manipulating the controllable release of the encapsulated anticancer drugs and photosensitizers for synergistic anticancer therapy remains a big challenge. In this study, a cancer cell-targeted, near-infrared (NIR) light-triggered and anticancer drug loaded liposome system (LPs) was developed for synergistic cancer therapy. Photosensitizer indocyanine green (ICG) and chemotherapy drug Curcumin (CUR) were coencapsulated into the liposomes, followed by the surface conjugation of GE11 peptide for epidermal growth factor receptor (EGFR) targeting on the cancer cell surface. Strictly controlled by NIR light, GE11 peptide modified and CUR/ICG-loaded LPs (GE11-CUR/ICG-LPs) could introduce hyperthermia in EGFR overexpressed A549 cancer cells for photothermal therapy, which could also trigger the increased release of CUR for enhanced cancer cell inhibition. GE11-CUR/ICG-LPs synergized photochemotherapy could induce reactive oxygen species (ROS) generation and cytoskeleton disruption to activate stronger apoptotic signaling events than the photothermal therapy or chemotherapy alone by regulating Bax/Bcl-2 and PI3K/AKT pathways. This EGFR-targeted drug-delivery nanosystem with NIR sensitivity may potentially serve in more effective anticancer therapeutics with reduced off-target effects.
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Li, Kaichun, Liying Pang, Xiaorong Pan, Shaonan Fan, Xinxin Wang, Qiaoyun Wang, Ping Dai, Wei Gao et Jie Gao. « GE11 Modified PLGA/TPGS Nanoparticles Targeting Delivery of Salinomycin to Breast Cancer Cells ». Technology in Cancer Research & ; Treatment 20 (1 janvier 2021) : 153303382110049. http://dx.doi.org/10.1177/15330338211004954.

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Salinomycin (Sal) is a potent inhibitor with effective anti-breast cancer properties in clinical therapy. The occurrence of various side effect of Sal greatly limits its application. The epidermal growth factor receptor (EGFR) family is a family of receptors highly expressed in most breast cancer cells. GE11 is a dodecapeptide which shows excellent EGFR affinity. A series of nanoparticles derivatives with GE11 peptide conjugated PLGA/TPGS were synthesized. Nanoprecipitation method was used to prepare the Sal loaded nanoparticles at the optimized concentration. The characterization, targeting efficacy, and antitumor activity were detected both in vitro and in vivo. Encapsulation of Sal in GE11 modified PLGA/TPGS nanoparticles shows an improved therapy efficacy and lower systemic side effect. This represents the delivery system a promising strategy to enhance the therapeutic effect against EGFR highly expressed breast cancer.
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Gimond, Clotilde, Arjan van der Flier, Sanne van Delft, Cord Brakebusch, Ingrid Kuikman, John G. Collard, Reinhard Fässler et Arnoud Sonnenberg. « Induction of Cell Scattering by Expression of β1 Integrins in β1-Deficient Epithelial Cells Requires Activation of Members of the Rho Family of Gtpases and Downregulation of Cadherin and Catenin Function ». Journal of Cell Biology 147, no 6 (13 décembre 1999) : 1325–40. http://dx.doi.org/10.1083/jcb.147.6.1325.

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Adhesion receptors, which connect cells to each other and to the surrounding extracellular matrix (ECM), play a crucial role in the control of tissue structure and of morphogenesis. In this work, we have studied how intercellular adhesion molecules and β1 integrins influence each other using two different β1-null cell lines, epithelial GE11 and fibroblast-like GD25 cells. Expression of β1A or the cytoplasmic splice variant β1D, induced the disruption of intercellular adherens junctions and cell scattering in both GE11 and GD25 cells. In GE11 cells, the morphological change correlated with the redistribution of zonula occluden (ZO)-1 from tight junctions to adherens junctions at high cell confluency. In addition, the expression of β1 integrins caused a dramatic reorganization of the actin cytoskeleton and of focal contacts. Interaction of β1 integrins with their respective ligands was required for a complete morphological transition towards the spindle-shaped fibroblast-like phenotype. The expression of an interleukin-2 receptor (IL2R)-β1A chimera and its incorporation into focal adhesions also induced the disruption of cadherin-based adhesions and the reorganization of ECM–cell contacts, but failed to promote cell migration on fibronectin, in contrast to full-length β1A. This indicates that the disruption of cell–cell adhesion is not simply the consequence of the stimulated cell migration. Expression of β1 integrins in GE11 cells resulted in a decrease in cadherin and α-catenin protein levels accompanied by their redistribution from the cytoskeleton-associated fraction to the detergent-soluble fraction. Regulation of α-catenin protein levels by β1 integrins is likely to play a role in the morphological transition, since overexpression of α-catenin in GE11 cells before β1 prevented the disruption of intercellular adhesions and cell scattering. In addition, using biochemical activity assays for Rho-like GTPases, we show that the expression of β1A, β1D, or IL2R-β1A in GE11 or GD25 cells triggers activation of both RhoA and Rac1, but not of Cdc42. Moreover, dominant negative Rac1 (N17Rac1) inhibited the disruption of cell–cell adhesions when expressed before β1. However, all three GTPases might be involved in the morphological transition, since expression of either N19RhoA, N17Rac1, or N17Cdc42 reversed cell scattering and partially restored cadherin-based adhesions in GE11-β1A cells. Our results indicate that β1 integrins regulate the polarity and motility of epithelial cells by the induction of intracellular molecular events involving a downregulation of α-catenin function and the activation of the Rho-like G proteins Rac1 and RhoA.
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Yang, Chengcheng, Xuan Mi, Huilan Su, Jingxing Yang, Yiyun Gu, Lu Zhang, Wenshe Sun, Xiaowen Liang et Chunfu Zhang. « GE11-PDA-Pt@USPIOs nano-formulation for relief of tumor hypoxia and MRI/PAI-guided tumor radio-chemotherapy ». Biomaterials Science 7, no 5 (2019) : 2076–90. http://dx.doi.org/10.1039/c8bm01492b.

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Lee, Duhwan, Yeong Mi Lee, Jihoon Kim, Myung Kyu Lee et Won Jong Kim. « Enhanced tumor-targeted gene delivery by bioreducible polyethylenimine tethering EGFR divalent ligands ». Biomaterials Science 3, no 7 (2015) : 1096–104. http://dx.doi.org/10.1039/c5bm00004a.

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Gaugaz, Fabienne, Andrea Chicca, Mariano Redondo-Horcajo, Isabel Barasoain, J. Díaz et Karl-Heinz Altmann. « Synthesis, Microtubule-Binding Affinity, and Antiproliferative Activity of New Epothilone Analogs and of an EGFR-Targeted Epothilone-Peptide Conjugate ». International Journal of Molecular Sciences 20, no 5 (5 mars 2019) : 1113. http://dx.doi.org/10.3390/ijms20051113.

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A new simplified, epoxide-free epothilone analog was prepared incorporating an N-(2-hydroxyethyl)-benzimidazole side chain, which binds to microtubules with high affinity and inhibits cancer cell growth in vitro with nM potency. Building on this scaffold, a disulfide-linked conjugate with the purported EGFR-binding (EGFR, epidermal growth factor receptor) peptide GE11 was then prepared. The conjugate retained significant microtubule-binding affinity, in spite of the size of the peptide attached to the benzimidazole side chain. The antiproliferative activity of the conjugate was significantly lower than for the parent scaffold and, surprisingly, was independent of the EGFR expression status of cells. Our data indicate that the disulfide-based conjugation with the GE11 peptide is not a viable approach for effective tumor-targeting of highly potent epothilones and probably not for other cytotoxics.
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Abourbeh, Galith, Alexei Shir, Eyal Mishani, Manfred Ogris, Wolfgang Rödl, Ernst Wagner et Alexander Levitzki. « PolyIC GE11 polyplex inhibits EGFR-overexpressing tumors ». IUBMB Life 64, no 4 (23 février 2012) : 324–30. http://dx.doi.org/10.1002/iub.1002.

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Oertel, F., F. Starke, W. Sihver, J. Steinbach et H. J. Pietzsch. « In vitro evaluation of 64Cu-labeled GE11-conjugates ». Nuclear Medicine and Biology 41, no 7 (août 2014) : 634–35. http://dx.doi.org/10.1016/j.nucmedbio.2014.05.035.

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Judmann, Benedikt, Björn Wängler, Ralf Schirrmacher, Gert Fricker et Carmen Wängler. « Towards Radiolabeled EGFR-Specific Peptides : Alternatives to GE11 ». Pharmaceuticals 16, no 2 (11 février 2023) : 273. http://dx.doi.org/10.3390/ph16020273.

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The human epidermal growth factor receptor (EGFR) is closely related to several cancer-promoting processes and overexpressed on a variety of tumor types, rendering it an important target structure for the imaging and therapy of several malignancies. To date, approaches to develop peptidic radioligands able to specifically address and visualize EGFR-positive tumors have been of limited success. Most of the attempts were based on the lead GE11, as this peptide was previously described to be a highly potent EGFR-specific agent. However, since it has recently been shown that GE11 exhibits an insufficient affinity to the EGFR in monomeric form to be suitable as a basis for the development of tracers based on it, in the present work we investigated which other peptides might be suitable as lead structures for the development of EGFR-specific peptidic radiotracers. For this purpose, we developed 68Ga-labeled radioligands based on the peptides D4, P1, P2, CPP, QRH, EGBP and Pep11, having been described before as EGFR-specific. In addition, we also tested three truncated versions of the endogenous EGFR ligand hEGF (human epidermal growth factor) with respect to their ability to specifically target the EGFR with high affinity. Therefore, chelator-modified labeling precursors of the mentioned peptides were synthesized, radiolabeled with 68Ga and the obtained radioligands were evaluated for their hydrophilicity/lipophilicity, stability against degradation by human serum peptidases, in vitro tumor cell uptake, and receptor affinity in competitive displacement experiments on EGFR-positive A431 cells. Although all NODA-GA-modified (NODA-GA: (1,4,7-triazacyclononane-4,7-diyl)diacetic acid-1-glutaric acid) labeling precursors could be obtained more or less efficient in yields between 5 and 74%, the 68Ga-radiolabeling proved to be unsuccessful for two of the three truncated versions of hEGF ([68Ga]Ga-8 and [68Ga]Ga-9), producing several side-products. For the other agents [68Ga]Ga-1–[68Ga]Ga-7, [68Ga]Ga-10 and [68Ga]Ga-11, high radiochemical yields and purities of ≥ 98% and molar activities of up to 114 GBq/µmol were obtained. In the assay investigating the radiopeptide susceptibilities against serum peptidase degradation, the EGBP-based agent demonstrated a limited stability with a half-life of only 66.4 ± 3.0 min, whereas the other tracers showed considerably higher stabilities of up to an 8000 min half-life. Finally, all radiotracer candidates were evaluated in terms of tumor cell internalization and receptor binding potential on EGFR-positive A431 cell. In these experiments, all developed agents failed to show an EGFR-specific tumor cell uptake or a relevant EGFR-affinity. By contrast, the positive controls tested under identical conditions, [125I]I-hEGF and hEGF demonstrated the expected high EGFR-specific tumor cell uptake (33.6% after 1 h, being reduced to 1.9% under blocking conditions) and affinity (IC50 value of 15.2 ± 3.3 nM). Thus, these results indicate that none of the previously described peptidic agents developed for EGFR targeting appears to be a reasonable choice as a lead structure for the development of radiopeptides for targeting of EGFR-positive tumors. Likewise, the tested truncated variants of the endogenous hEGF do not seem to be promising alternatives for this purpose.
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Luo, H. B., X. B. Li, Q. E. Zhang, M. D. Chen et Y. K. Cheng. « A density functional theory study of germanium Ge11 clusters ». Journal of Molecular Structure : THEOCHEM 674, no 1-3 (avril 2004) : 83–86. http://dx.doi.org/10.1016/j.theochem.2004.01.010.

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Soleymani Abyaneh, Hoda, Amir Soleimani, Mohammad Vakili, Rania Soudy, Kamaljit Kaur, Francesco Cuda, Ali Tavassoli et Afsaneh Lavasanifar. « Modulation of Hypoxia-Induced Chemoresistance to Polymeric Micellar Cisplatin : The Effect of Ligand Modification of Micellar Carrier Versus Inhibition of the Mediators of Drug Resistance ». Pharmaceutics 10, no 4 (21 octobre 2018) : 196. http://dx.doi.org/10.3390/pharmaceutics10040196.

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Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(α-carboxyl-ε-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and cisplatin micelles in MDA-MB-231 cells. A significant increase in micellar cisplatin uptake was observed in MDA-MB-231 cells that overexpress EGFR, following surface modification of micelles with GE11. This did not lead to increased cytotoxicity of micellar cisplatin, however. On the other hand, the addition of pharmacological inhibitors of key molecules involved in HICR in MDA-MB-231 cells, i.e., inhibitors of hypoxia inducing factor-1 (HIF-1) and signal transducer and activator of transcription 3 (STAT3), substantially enhanced the cytotoxicity of free and cisplatin micelles. The results indicated the potential benefit of combination therapy with HIF-1 and STAT3 inhibitors in overcoming HICR to free or micellar cisplatin.
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Quinn, Jeffrey A., C. Thomas Graeber, A. Raymond Frackelton, Minsoo Kim, Jean E. Schwarzbauer et Edward J. Filardo. « Coordinate Regulation of Estrogen-Mediated Fibronectin Matrix Assembly and Epidermal Growth Factor Receptor Transactivation by the G Protein-Coupled Receptor, GPR30 ». Molecular Endocrinology 23, no 7 (1 juillet 2009) : 1052–64. http://dx.doi.org/10.1210/me.2008-0262.

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Abstract Estrogen promotes changes in cytoskeletal architecture not easily attributed to the biological action of estrogen receptors, ERα and ERβ. The Gs protein-coupled transmembrane receptor, GPR30, is linked to specific estrogen binding and rapid estrogen-mediated release of heparin-bound epidermal growth factor. Using marker rescue and dominant interfering mutant strategies, we show that estrogen action via GPR30 promotes fibronectin (FN) matrix assembly by human breast cancer cells. Stimulation with 17β-estradiol or the ER antagonist, ICI 182, 780, results in the recruitment of FN-engaged integrin α5β1 conformers to fibrillar adhesions and the synthesis of FN fibrils. Concurrent with this cellular response, GPR30 promotes the formation of Src-dependent, Shc-integrin α5β1 complexes. Function-blocking antibodies directed against integrin α5β1 or soluble Arg-Gly-Asp peptide fragments derived from FN specifically inhibited GPR30-mediated epidermal growth factor receptor transactivation. Estrogen-mediated FN matrix assembly and epidermal growth factor receptor transactivation were similarly disrupted in integrin β1-deficient GE11 cells, whereas reintroduction of integrin β1 into GE11 cells restored these responses. Mutant Shc (317Y/F) blocked GPR30-induced FN matrix assembly and tyrosyl phosphorylation of erbB1. Interestingly, relative to recombinant wild-type Shc, 317Y/F Shc was more readily retained in GPR30-induced integrin α5β1 complexes, yet this mutant did not prevent endogenous Shc-integrin α5β1 complex formation. Our results suggest that GPR30 coordinates estrogen-mediated FN matrix assembly and growth factor release in human breast cancer cells via a Shc-dependent signaling mechanism that activates integrin α5β1.
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Biscaglia, Francesca, Senthilkumar Rajendran, Paolo Conflitti, Clara Benna, Roberta Sommaggio, Lucio Litti, Simone Mocellin et al. « Enhanced EGFR Targeting Activity of Plasmonic Nanostructures with Engineered GE11 Peptide ». Advanced Healthcare Materials 6, no 23 (25 septembre 2017) : 1700596. http://dx.doi.org/10.1002/adhm.201700596.

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Jiao, Honglei, Xinming Zhao, Jingya Han, Jingmian Zhang et Jianfang Wang. « Synthesis of a novel 99mTc labeled GE11 peptide for EGFR SPECT imaging ». International Journal of Radiation Biology 96, no 11 (1 septembre 2020) : 1443–51. http://dx.doi.org/10.1080/09553002.2020.1811419.

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Grataitong, Khwanthana, Wattana Weerachatyanukul, Krittalak Chakrabandhu et Anne-Odile Hueber. « Modified MrNV viral capsids with GE11 peptide for binding colorectal cancer cells. » FASEB Journal 34, S1 (avril 2020) : 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.09231.

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Dissoki, Samar, Aviv Hagooly, Smadar Elmachily et Eyal Mishani. « Labeling approaches for the GE11 peptide, an epidermal growth factor receptor biomarker ». Journal of Labelled Compounds and Radiopharmaceuticals 54, no 11 (18 août 2011) : 693–701. http://dx.doi.org/10.1002/jlcr.1910.

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Abdulmalek, Shaymaa, Nouf Mostafa, Marwa Gomaa, Mohamed El‑Kersh, Ayman I. Elkady et Mahmoud Balbaa. « Bee venom-loaded EGFR-targeting peptide-coupled chitosan nanoparticles for effective therapy of hepatocellular carcinoma by inhibiting EGFR-mediated MEK/ERK pathway ». PLOS ONE 17, no 8 (10 août 2022) : e0272776. http://dx.doi.org/10.1371/journal.pone.0272776.

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Hepatocellular carcinoma (HCC) is one of the world’s most risky diseases due to the lack of clear and cost-effective therapeutic targets. Currently, the toxicity of conventional chemotherapeutic medications and the development of multidrug resistance is driving research into targeted therapies. The nano-biomedical field’s potential for developing an effective therapeutic nano-sized drug delivery system is viewed as a significant pharmaceutical trend for the encapsulation and release of numerous anticancer therapies. In this regard, current research is centered on the creation of biodegradable chitosan nanoparticles (CSNPs) for the selective and sustained release of bee venom into liver cancer cells. Furthermore, surface modification with polyethylene glycol (PEG) and GE11 peptide-conjugated bee venom-CSNPs allows for the targeting of EGFR-overexpressed liver cancer cells. A series of in vitro and in vivo cellular analyses were used to investigate the antitumor effects and mechanisms of targeted bee venom-CSNPs. Targeted bee venom-CSNPs, in particular, were found to have higher cytotoxicity against HepG2 cells than SMMC-7721 cells, as well as stronger cellular uptake and a substantial reduction in cell migration, leading to improved cancer suppression. It also promotes cancer cell death in EGFR overexpressed HepG2 cells by boosting reactive oxygen species, activating mitochondria-dependent pathways, inhibiting EGFR-stimulated MEK/ERK pathway, and elevating p38-MAPK in comparison to native bee venom. In hepatocellular carcinoma (HCC)-induced mice, it has anti-cancer properties against tumor tissue. It also improved liver function and architecture without causing any noticeable toxic side effects, as well as inhibiting tumor growth by activating the apoptotic pathway. The design of this cancer-targeted nanoparticle establishes GE11-bee venom-CSNPs as a potential chemotherapeutic treatment for EGFR over-expressed malignancies. Finally, our work elucidates the molecular mechanism underlying the anticancer selectivity of targeted bee venom-CSNPs and outlines therapeutic strategies to target liver cancer.
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Zain, Mohd Izani Mohd, et Mohd Daud Mat Din. « Democratic Dilemma of Malay Islamic Party : PAS, Coalition Pattern, and Rising Social Issues ». Studia Islamika 29, no 1 (22 juin 2022) : 83–109. http://dx.doi.org/10.36712/sdi.v29i1.16330.

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This article deliberates on how the Pan-Malaysian Islamic Party (PAS) embraces and weathers the challenges of democracy as a political culture beyond elections. The deliberation analyses the approach and behaviors of the party within a period of three general elections (GE), namely the GE12 in 2008, GE13 in 2013, and GE14 in 2018. Through qualitative approach and in-depth interviews with key PAS leaders, this article discusses PAS participation with the Pakatan Rakyat (PR), Muafakat Nasional (MN), and Perikatan Nasional (PN), which demonstrated the PAS’s unchartered undertaking to accept democracy as a political culture and not as a tool to achieve political power through an election. While it is trite to take the position that elections are the truest form of democracy, they can foster greater inclusivity, which can take place in both political and non-political realms.
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Nadzri, Muhamad M. N. « The 14th General Election, the Fall of Barisan Nasional, and Political Development in Malaysia, 1957-2018 ». Journal of Current Southeast Asian Affairs 37, no 3 (décembre 2018) : 139–71. http://dx.doi.org/10.1177/186810341803700307.

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The results of the recent 2018 general election (GE14) in Malaysia were exceptional. The ruling party – Barisan Nasional (BN) – was ousted from power after over six decades of authoritarian rule, by a new opposition coalition – the Pakatan Harapan (PH). In this historic election, BN lost all the federal states in Peninsular Malaysia except for the two less developed ones of Perlis and Pahang. BN was also defeated in Sabah for the second time since its dramatic recapture in 1995. However, these results are not as surprising if one looks at the outcome from its historical and developmental perspectives. The indication of the breakdown of the one-party dominant state of Malaysia can (at least) be traced back to 10 years ago – since the 2008 general election (GE12). BN then lost several parliamentary seats in the urban centres, even with a less unified opposition. It had also lost four states on the west coast of Peninsular Malaysia, and had been fairly incompetent in reclaiming control over Selangor and Penang since that particular election. Five years later, in the 2013 general election (GE13), the results aggravated BN. It had lost its popular votes to the then opposition coalition – the Pakatan Rakyat (PR). The main objectives of this article, therefore, are twofold. First, it intends to shed light on the recent general elections through historical and developmental approaches by linking them to the electoral results, and political development in Malaysia, respective to GE12 and GE13. Second, it strives to make available for analysis the arguments on how the opposition pact managed to unseat BN in GE14. The analysis in this article is based on the data gathered by the author through a mixture of media studies, library research, and direct observation – as this author was one of the official observers appointed by the Election Commission of Malaysia for GE14. The main argument of this article on the breakthrough of PH to the federal government is that the opposition managed to reshape the multiparty electoral system to a “two-plus-one party system” from late 2016, which boosted the level of political competition between the two main parties in Malaysia – namely, BN and PH – in GE14. Four major factors have been identified as constituting the triumph of PH and the fall of BN in the election. These are: the existence of a credible representative and strong opposition, with the inclusion of Mahathir and two Malay/ Bumiputra (“the natives”) political parties; the rupture of the elites within the ruling regime; the presence of impactful issues surrounding Najib's administration; and, the advancement of information and communications technology as well as its impact on the emergence of a digital and much more participative society in Malaysia.
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Liu, Zhuo-Yan, Guang-Hai Yan, Xiao-Yu Li, Zhuo Zhang, Yu-Zhu Guo, Kai-Xuan Xu, Ji-Shan Quan et Guang-Yu Jin. « GE11 peptide modified CSO-SPION micelles for MRI diagnosis of targeted hepatic carcinoma ». Biotechnology & ; Biotechnological Equipment 35, no 1 (1 janvier 2021) : 1574–86. http://dx.doi.org/10.1080/13102818.2021.1997154.

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Rahmanian, Najmeh, Seyed Jalal Hosseinimehr, Ali Khalaj, Zohreh Noaparast, Seyed Mohammad Abedi et Omid Sabzevari. « 99mTc labeled HYNIC-EDDA/tricine-GE11 peptide as a successful tumor targeting agent ». Medicinal Chemistry Research 27, no 3 (15 novembre 2017) : 890–902. http://dx.doi.org/10.1007/s00044-017-2111-7.

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Bouhali, O., V. Bhatnagar, A. Castaneda, S. S. Chauhan, T. Kamon, Y. Kang, S. Kumar et A. K. Virdi. « Radiation background estimation for the GE11 Triple-GEM detectors in the CMS endcap ». Journal of Physics : Conference Series 2374, no 1 (1 novembre 2022) : 012161. http://dx.doi.org/10.1088/1742-6596/2374/1/012161.

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The Compact Muon Solenoid (CMS) is a general-purpose particle detector at the Large Hadron Collider (LHC) designed to study a wide range of particles produced in high energy collisions. The interaction of the beams with the pipe, shielding and detector supporting materials can produce neutrons, photons, electrons and positrons, forming a common background radiation field for CMS detector. A Monte-Carlo simulation is used to predict the background rate for a newly installed detector. In the forward region, the upgrade includes Gas Electron Multiplier (GEM) detectors called GE1/1. In this study, an estimate of the GE1/1 detector response to the background radiation is presented. The flux of background radiation is predicted using the FLUKA framework and the response of the detector is predicted using the GEANT4 framework. A comparison with actual GEM slice data is used as validation.
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Lunsford, Dale L. « Exploring Students' Perceptions of the Web as an Information Source ». Journal of Educational Technology Systems 27, no 4 (juin 1999) : 337–47. http://dx.doi.org/10.2190/ge11-34cn-adlt-py3x.

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King, R. Bruce. « Trivalent Polyhedra as Duals of Borane Deltahedra : From Molecular Endohedral Germanium Clusters to the Smallest Fullerenes ». Molecules 28, no 2 (4 janvier 2023) : 496. http://dx.doi.org/10.3390/molecules28020496.

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The duals of the most spherical closo borane deltahedra having from 6 to 16 vertices form a series of homologous spherical trivalent polyhedra with even numbers of vertices from 8 to 28. This series of homologous polyhedra is found in endohedral clusters of the group 14 atoms such as the endohedral germanium cluster anions [M@Ge10]3– (M = Co, Fe) and [Ru@Ge12]3– The next members of this series have been predicted to be the lowest energy structures of the endohedral silicon clusters Cr@Si14 and M@Si16 (M = Zr, Hf). The largest members of this series correspond to the smallest fullerene polyhedra found in the endohedral fullerenes M@C28 (M = Zr, Hf, Th, U). The duals of the oblate (flattened) ellipsoidal deltahedra found in the dirhenaboranes Cp*2Re2Bn–2Hn–2 (Cp* = h5-Me5C5; 8 ≤ n ≤ 12) are prolate (elongated) trivalent polyhedra as exemplified experimentally by the germanium cluster [Co2@Ge16]4– containing an endohedral Co2 unit.
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Hailing, Tang, Pan Yonghong, Zhang Yufeng et Tang Haitao. « Challenges for the application of EGFR-targeting peptide GE11 in tumor diagnosis and treatment ». Journal of Controlled Release 349 (septembre 2022) : 592–605. http://dx.doi.org/10.1016/j.jconrel.2022.07.018.

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T. DeJesus, Onofre. « Synthesis of [64Cu]Cu-NOTA-Bn-GE11 for PET Imaging of EGFR-Rich Tumors ». Current Radiopharmaceuticalse 5, no 1 (1 janvier 2012) : 15–18. http://dx.doi.org/10.2174/1874471011205010015.

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Chen, Chien-Jen, Chen-Hsin Chan, Kun-Liang Lin, Jyun-Hong Chen, Chun-Hao Tseng, Ping-Yen Wang, Chuan-Yi Chien, Hung-Man Yu et Wuu-Jyh Lin. « 68Ga-labelled NOTA-RGD-GE11 peptide for dual integrin and EGFR-targeted tumour imaging ». Nuclear Medicine and Biology 68-69 (janvier 2019) : 22–30. http://dx.doi.org/10.1016/j.nucmedbio.2018.11.003.

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Tang, Hailing, Xiaojing Chen, Mengjie Rui, Wenqiang Sun, Jian Chen, Jinliang Peng et Yuhong Xu. « Effects of Surface Displayed Targeting Ligand GE11 on Liposome Distribution and Extravasation in Tumor ». Molecular Pharmaceutics 11, no 10 (12 septembre 2014) : 3242–50. http://dx.doi.org/10.1021/mp5001718.

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Striese, Franziska, Wiebke Sihver, Feng Gao, Ralf Bergmann, Martin Walther, Jens Pietzsch, Jörg Steinbach et Hans-Jürgen Pietzsch. « Exploring pitfalls of 64Cu-labeled EGFR-targeting peptide GE11 as a potential PET tracer ». Amino Acids 50, no 10 (23 juillet 2018) : 1415–31. http://dx.doi.org/10.1007/s00726-018-2616-5.

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Koay, Hean Wei, et Salwa Mokhtar Khairiah. « The role of political marketing and its importance in Barisan Nasional at Malaysia general election ». Technium Social Sciences Journal 29 (9 mars 2022) : 548–60. http://dx.doi.org/10.47577/tssj.v29i1.6138.

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This study discusses the political marketing tools based on the research in Barisan Nasional (BN) at Malaysia general election. According to the Malaysian law, the date of the last election and subsequent election is to be held at 5-year intervals. Thus, after GE12 in 2008, GE13 was held in 2013. Since 1969 from Alliance coalition to 1973 BN coalition never lost a general election in parliamentary constituency. The political tsunami in GE12 BN won 140 seats in Dewan Rakyat out of 222 seats, opposition parties such as Pakatan Rakyat (PR) won 82 seats out of 222 Dewan Rakyat of seats in Malaysia (Election Commission of Malaysia, 2008, 2013, 2018). The GE13 result was almost the same as GE12 in which BN won 133 seats in Dewan Rakyat or 47.38% of the votes. Pakatan Rakyat (PR) won the support for 89 seats in Dewan Rakyat or 50.87% of the votes. This is first time BN won in the general election but with less of the votes. In GE12 and GE13 voters started to support the opposition rather than BN. Specifically, direct voter contact, indirect voter contact, dominant party, party leader, gerrymandering, malapportionment, re-delineation, first-past-the-post system (FPTP) are the political marketing tools implement by BN. This paper discusses about political marketing tools employed by BN during general election. Therefore, this paper can provide information to political parties and help them to identify the suitable political marketing tools for coming elections.
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Adem, B., A. L. Teixeira, F. Dias, C. Ruivo, R. Medeiros et S. A. Melo. « GE11 positive exosomes as a potential RNAi delivery system in clear cell Renal Cell Carcinoma ». Porto Biomedical Journal 2, no 5 (septembre 2017) : 181. http://dx.doi.org/10.1016/j.pbj.2017.07.016.

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Iijima, Junko, Yanyang Zhao, Tomoya Isaji, Akihiko Kameyama, Shuuichi Nakaya, Xiangchun Wang, Hideyuki Ihara et al. « Cell-Cell Interaction-dependent Regulation ofN-Acetylglucosaminyltransferase III and the BisectedN-Glycans in GE11 Epithelial Cells ». Journal of Biological Chemistry 281, no 19 (14 mars 2006) : 13038–46. http://dx.doi.org/10.1074/jbc.m601961200.

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Xu, Qingsong, Chen Qu, Wenjing Wang, Jianguo Gu, Yuguang Du et Linsheng Song. « SpecificN-glycan alterations are coupled in epithelial-mesenchymal transition induced by EGF in GE11 epithelial cells ». Cell Biology International 41, no 2 (29 décembre 2016) : 124–33. http://dx.doi.org/10.1002/cbin.10707.

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Haddick, Lisa, Wei Zhang, Sören Reinhard, Karin Möller, Hanna Engelke, Ernst Wagner et Thomas Bein. « Particle-Size-Dependent Delivery of Antitumoral miRNA Using Targeted Mesoporous Silica Nanoparticles ». Pharmaceutics 12, no 6 (2 juin 2020) : 505. http://dx.doi.org/10.3390/pharmaceutics12060505.

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Multifunctional core-shell mesoporous silica nanoparticles (MSN) were tailored in size ranging from 60 to 160 nm as delivery agents for antitumoral microRNA (miRNA). The positively charged particle core with a pore diameter of about 5 nm and a stellate pore morphology allowed for an internal, protective adsorption of the fragile miRNA cargo. A negatively charged particle surface enabled the association of a deliberately designed block copolymer with the MSN shell by charge-matching, simultaneously acting as a capping as well as endosomal release agent. Furthermore, the copolymer was functionalized with the peptide ligand GE11 targeting the epidermal growth factor receptor, EGFR. These multifunctional nanoparticles showed an enhanced uptake into EGFR-overexpressing T24 bladder cancer cells through receptor-mediated cellular internalization. A luciferase gene knock-down of up to 65% and additional antitumoral effects such as a decreased cell migration as well as changes in cell cycle were observed. We demonstrate that nanoparticles with a diameter of 160 nm show the fastest cellular internalization after a very short incubation time of 45 min and produce the highest level of gene knock-down.
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Xu, Wei-Wei, Da-yu Liu, Ying-chun Cao et Xiang-yun Wang. « GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers ». International Journal of Nanomedicine Volume 12 (septembre 2017) : 6461–70. http://dx.doi.org/10.2147/ijn.s129946.

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Zou, Yan, Yifeng Xia, Fenghua Meng, Jian Zhang et Zhiyuan Zhong. « GE11-Directed Functional Polymersomal Doxorubicin as an Advanced Alternative to Clinical Liposomal Formulation for Ovarian Cancer Treatment ». Molecular Pharmaceutics 15, no 9 (23 mars 2018) : 3664–71. http://dx.doi.org/10.1021/acs.molpharmaceut.8b00024.

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Hui, Hon Chung. « Were Foreign Exchange Markets Reacting Negatively to Political Events ? The Case of Malaysia ». South Asian Journal of Macroeconomics and Public Finance 10, no 1 (1 avril 2021) : 105–29. http://dx.doi.org/10.1177/2277978721995649.

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This article explores the effects of political events on foreign exchange returns in Malaysia. We identify five political events in recent history, namely the 13th General Election (GE13), the imprisonment of a key opposition politician, the scandal from the 1MDB exposé, the appointment of a new Central Bank Governor and the 14th General Election (GE14). Using event studies, our findings show that the imprisonment of the opposition party leader triggered a favourable response from the foreign exchange market. However, market reactions to the 1MDB scandal were largely unfavourable. The GE13 triggered unfavourable market response, while the reverse is true for market reactions to GE14. Market response to the appointment of the new Central Bank Governor was rather positive. The Event Study is the first of its kind that examines the foreign exchange market implications of key political events in Malaysia. There are practical considerations that emanate from these findings. JEL Classification: F31, D72, D73, O38
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Xin, Xiaofei, Virender Kumar, Feng Lin, Vinod Kumar, Rajan Bhattarai, Vijaya R. Bhatt, Chalet Tan et Ram I. Mahato. « Redox-responsive nanoplatform for codelivery of miR-519c and gemcitabine for pancreatic cancer therapy ». Science Advances 6, no 46 (novembre 2020) : eabd6764. http://dx.doi.org/10.1126/sciadv.abd6764.

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Desmoplastic and hypoxic pancreatic cancer microenvironment induces aberrant expression of miRNAs and hypoxia-inducible factor-1α (HIF-1α) responsible for gemcitabine (GEM) resistance. We demonstrated that miR-519c was down-regulated in pancreatic cancer and transfection of miR-519c in GEM-resistant pancreatic cancer cells inhibited HIF-1α level under hypoxia. We synthesized redox-sensitive mPEG-co-P(Asp)-g-DC-g-S-S-GEM polymer, with GEM payload of 14% (w/w) and 90% GEM release upon incubation with l-glutathione. We synthesized mPEG-co-P(Asp)-g-TEPA-g-DC for complex formation with miRNA. Chemical modification of miR-519c with 2′-O-methyl phosphorothioate (OMe-PS) at 3′ end enhanced its stability and activity without being immunogenic. Epidermal growth factor receptor targeting peptide GE11 decoration increased tumor accumulation of micelles after systemic administration and significantly inhibited orthotopic desmoplastic pancreatic cancer growth in NSG mice by down-regulating HIF-1α and genes responsible for glucose uptake and cancer cell metabolism. Our multifunctional nanomedicine of GEM and OMe-PS–miR-519c offers a novel therapeutic strategy to treat desmoplasia and hypoxia-induced chemoresistance in pancreatic cancer.
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Zhou, Cheng, Yifeng Xia, Yaohua Wei, Liang Cheng, Jingjing Wei, Beibei Guo, Fenghua Meng, Shoupeng Cao, Jan C. M. van Hest et Zhiyuan Zhong. « GE11 peptide-installed chimaeric polymersomes tailor-made for high-efficiency EGFR-targeted protein therapy of orthotopic hepatocellular carcinoma ». Acta Biomaterialia 113 (septembre 2020) : 512–21. http://dx.doi.org/10.1016/j.actbio.2020.06.020.

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Hu, Danrong, Omar Mezghrani, Lei Zhang, Yi Chen, Xue Ke et Tianyuan Ci. « GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy ». International Journal of Nanomedicine Volume 11 (octobre 2016) : 5125–47. http://dx.doi.org/10.2147/ijn.s113469.

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Yu, Hung-Man, Jyun-Hong Chen, Kun-Liang Lin et Wuu-Jyh Lin. « Synthesis of68Ga-labeled NOTA-RGD-GE11 heterodimeric peptide for dual integrin and epidermal growth factor receptor-targeted tumor imaging ». Journal of Labelled Compounds and Radiopharmaceuticals 58, no 7 (21 mai 2015) : 299–303. http://dx.doi.org/10.1002/jlcr.3296.

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Li, Xueli, Kongzhen Hu, Wenfeng Liu, Yuanfeng Wei, Runhua Sha, Yongxuan Long, Yanjiang Han et al. « Synthesis and evaluation of [18F]FP-Lys-GE11 as a new radiolabeled peptide probe for epidermal growth factor receptor (EGFR) imaging ». Nuclear Medicine and Biology 90-91 (novembre 2020) : 84–92. http://dx.doi.org/10.1016/j.nucmedbio.2020.10.004.

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Paiva, Igor, Stephanie Mattingly, Melinda Wuest, Samantha Leier, Mohammad Reza Vakili, Michael Weinfeld, Afsaneh Lavasanifar et Frank Wuest. « Synthesis and Analysis of 64Cu-Labeled GE11-Modified Polymeric Micellar Nanoparticles for EGFR-Targeted Molecular Imaging in a Colorectal Cancer Model ». Molecular Pharmaceutics 17, no 5 (1 avril 2020) : 1470–81. http://dx.doi.org/10.1021/acs.molpharmaceut.9b01043.

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Carmona-Ule, Nuria, Noga Gal, Carmen Abuín Redondo, María De La Fuente Freire, Rafael López López et Ana Belén Dávila-Ibáñez. « Peptide-Functionalized Nanoemulsions as a Promising Tool for Isolation and Ex Vivo Culture of Circulating Tumor Cells ». Bioengineering 9, no 8 (10 août 2022) : 380. http://dx.doi.org/10.3390/bioengineering9080380.

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Circulating Tumor Cells (CTCs) are shed from primary tumors and travel through the blood, generating metastases. CTCs represents a useful tool to understand the biology of metastasis in cancer disease. However, there is a lack of standardized protocols to isolate and culture them. In our previous work, we presented oil-in-water nanoemulsions (NEs) composed of lipids and fatty acids, which showed a benefit in supporting CTC cultures from metastatic breast cancer patients. Here, we present Peptide-Functionalized Nanoemulsions (Pept-NEs), with the aim of using them as a tool for CTC isolation and culture in situ. Therefore, NEs from our previous work were surface-decorated with the peptides Pep10 and GE11, which act as ligands towards the specific cell membrane proteins EpCAM and EGFR, respectively. We selected the best surface to deposit a layer of these Pept-NEs through a Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method. Next, we validated the specific recognition of Pept-NEs for their protein targets EpCAM and EGFR by QCM-D and fluorescence microscopy. Finally, a layer of Pept-NEs was deposited in a culture well-plate, and cells were cultured on for 9 days in order to confirm the feasibility of the Pept-NEs as a cell growth support. This work presents peptide-functionalized nanoemulsions as a basis for the development of devices for the isolation and culture of CTCs in situ due to their ability to specifically interact with membrane proteins expressed in CTCs, and because cells are capable of growing on top of them.
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Colzani, Barbara, Giovanna Speranza, Rossella Dorati, Bice Conti, Tiziana Modena, Giovanna Bruni, Elisa Zagato et al. « Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs : synthesis, preparation and in vitro/ex vivo characterization ». International Journal of Pharmaceutics 511, no 2 (septembre 2016) : 1112–23. http://dx.doi.org/10.1016/j.ijpharm.2016.08.011.

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Pi, Jiang, Jinhuan Jiang, Huaihong Cai, Fen Yang, Hua Jin, Peihui Yang, Jiye Cai et Zheng W. Chen. « GE11 peptide conjugated selenium nanoparticles for EGFR targeted oridonin delivery to achieve enhanced anticancer efficacy by inhibiting EGFR-mediated PI3K/AKT and Ras/Raf/MEK/ERK pathways ». Drug Delivery 24, no 1 (1 janvier 2017) : 1549–64. http://dx.doi.org/10.1080/10717544.2017.1386729.

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Yabe, Ayaka, et Shuh-ichi Nishikawa. « Expression of GEX1 Orthologs of Brassica rapa and Oryza sativa Rescued the Nuclear Fusion Defect of the Arabidopsis GEX1 Mutant ». Plants 11, no 14 (8 juillet 2022) : 1808. http://dx.doi.org/10.3390/plants11141808.

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Nuclear fusion is required for the sexual reproduction of various organisms, including angiosperms. During the life cycle of angiosperms, nuclear fusion occurs three times: once during female gametogenesis, when the two polar nuclei fuse in the central cell, and twice during double fertilization. Nuclear fusion in plant reproduction is achieved by sequential nuclear fusion events: outer and inner nuclear membrane fusion. Arabidopsis gamete expressed 1 (GEX1) is a nuclear membrane protein of gametes that is required for nuclear fusion during reproduction. Although orthologs of GEX1 have been identified in various land plants, sequence identities are not high, even between angiosperm GEX1 orthologs; the sequence identity between Arabidopsis GEX1 and Oryza sativa GEX1 ortholog is lower than 50%. Here, we found that the expression of GEX1 orthologs of O. sativa, as well as of Brassica rapa from the Arabidopsis GEX1 promoter, rescued the polar nuclear fusion defect of the gex1 mutant. We also found that the expression of these GEX1 orthologs rescued the lethality of the gex1 homozygous mutant, which is proposed to be caused by the sperm nuclear fusion defects upon fertilization. Our results indicate a functional conservation between Arabidopsis and O. sativa GEX1 orthologs, despite their relatively low sequence identities.
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Ramadhan bin Ibrahim, Muhammad Akram, Pah Chin Hee, Mohd Aminul Islam et Hafizah Bahaludin. « Cooperative Game Theory Approach for Portfolio Sectoral Selection Before and After Malaysia General Elections : GE13 versus GE14 ». Saudi Journal of Economics and Finance 4, no 8 (11 août 2020) : 390–99. http://dx.doi.org/10.36348/sjef.2020.v04i08.003.

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Gomez, James, et Rusdi Omar. « Overseas Voter Mobilisation in Singapore : Implications from Malaysia's 13th General Election ». Journal of Current Southeast Asian Affairs 32, no 2 (août 2013) : 105–23. http://dx.doi.org/10.1177/186810341303200206.

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This paper discusses voter mobilisation and other election-related activities of Malaysian voters living, studying and working in Singapore in the context of Malaysia's 13th general election (GE13). According to the World Bank, nearly 400,000 Malaysians reside in the city-state. Thus these figures represent a significant Malaysian voter pool based in Singapore. Efforts to mobilise these voters for general elections or other causes have political implications for both countries, which became apparent following Singapore-based Malaysians’ activities to encourage Malaysians to return home to cast their votes during the 13th general election. Singapore's strict public assembly laws led to several legal issues related to the voter mobilisation and election campaign activities undertaken by Malaysians in the city-state. These legal issues became a source of friction between the two countries during the elections as government leaders and authorities on both sides of the causeway accused the other of interfering in domestic political matters. Given the growing number of Malaysians in Singapore and the likely repeat of Malaysian voter mobilisation activities in Singapore in the run-up to the fourteenth general election (GE14) in 2018, issues related to the election activities of Malaysian voters in Singapore stand to be another set of factors that will shape the health of bilateral relations between these two countries.
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