Search results for "t7"
showing 10 items of 30 documents
Irreversible Inhibition of Epidermal Growth Factor Receptor Activity by 3-Aminopropanamides
2012
Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off-targets. We describe here a new series of irreversible inhibitors containing a 3-aminopropanamide linked in position 6 to 4-anilinoquinazoline or 4-anilinoquinoline-3- carbonitrile driving portions. Some of these compounds proved to be as efficient as their acrylamide analogues in inhibiting EGFR-TK (TK = tyrosine kinase) autophosphorylati…
Electrochemical probe for the monitoring of DNA-protein interactions.
2010
Self-assembly of thiol-terminated oligonucleotides on gold substrates provides a convenient way for DNA-functionalized surfaces. Here we describe the development of an electrochemical assay for the detection of DNA-protein interactions based on the modification of the electrochemical response of methylene blue (MB) intercalated in the DNA strands. Using a functionalized electrode with double stranded DNA carrying T3 RNA polymerase binding sequence, we show a substantial attenuation of the current upon the DNA-protein interaction. Moreover, a Langmuir binding isotherm for T3 RNA polymerase (T3 Pol) gives a dissociation constant K(D) equal to 0.46+/-0.23 microM. Such value is 100 times lower …
Efectos del desarrollo sostenible percibido por el consumidor. Una propuesta de modelo de hipermercados en Ecuador
2020
Resumen El objetivo de este trabajo fue analizar la incidencia del desarrollo sostenible sobre la cadena de efectos: valor percibido - capital de marca - lealtad. Para ello, se propone un modelo teórico de relaciones que se contrasta a partir de una muestra de 317 clientes de hiper mercados en Ecuador. Los resultados, aplicando una metodología exploratoria y confirmatoria, combinada con regresión por mínimos cuadrados parciales, mostraron que tanto las acciones de desarrollo sostenible como el valor percibido son pilares maestros sobre los que se puede apoyar la estrategia minorista. Ambas se muestran como variables clave por su naturaleza, en cuanto son multidimensio nales, y por su alcanc…
Abstract LB-399: Chronic inhibition of mutant EGFR in NSCLC leads to EGFR TKI resistance by TGF-β1 mediated epithelial to mesenchymal transition
2011
Abstract In NSCLC, activating EGFR mutations underlie responsiveness of NSCLCs to reversible EGFR tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib. Despite initial responses, acquired resistance invariably develops, mediated by the emergence of the secondary T790M mutation and by focal amplification of MET, in approximately 50% and 30% of patients, respectively. The resistance mechanisms for the remaining 20% of cases remain elusive. EGFR TKI-sensitive HCC827 cells were exposed to graded concentrations of erlotinib for 6 months. Approximately 70% of the isolated clones were resistant to erlotinib and harbored MET amplification, and were sensitive to dual EGFR/MET inhibit…
Abstract 766: Suppression of gefitinib-induced EMT in EGFR mutant NSCLC preferentially selects for acquired T790M
2015
Abstract Activating EGFR mutations in non-small lung cancer (NSCLC) confer sensitivity to reversible EGFR tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib. Despite promising initial response acquired resistance develops mediated by the emergence of the secondary T790M mutation or by focal amplification of MET. An epithelial-to-mesenchymal transition (EMT) is clinically linked to NSCLCs with acquired EGFR TKI resistance. The exact mechanisms of EGFR TKI resistance with EMT phenotype remain elusive; therefore, we attempted to develop a strategy to prevent the emergence of EGFR TKI resistance with EMT phenotype. In order to mimic the development of acquired EGFR TKI resista…
Abstract LB-C21: CXCR7 expression is necessary for the maintenance of mesenchymal phenotype in acquired EGFR TKI resistance in NSCLC
2015
Abstract Activating EGFR mutations in non-small lung cancer (NSCLC) confer sensitivity to reversible EGFR tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib. Despite promising initial response, acquired resistance develops mediated by the emergence of the secondary T790M mutation or by focal amplification of MET. An epithelial-to-mesenchymal transition (EMT) is clinically linked to NSCLCs with acquired EGFR TKI resistance. The exact mechanisms of EGFR TKI resistance with EMT phenotype remain elusive; therefore, we have engineered EGFR-mutated NSCLC cell lines with mesenchymal phenotype by stably depleting E-Cadherin or by overexpressing Snail or chronically exposing the ce…
Symmetric expansion of neural stem cells from the adult olfactory bulb is driven by astrocytes via WNT7A.
2012
Adult neural stem cells (NSCs) located in the subventricular zone (SVZ) persistently produce new neurons destined to the olfactory bulb (OB). Recent research suggests that the OB is also a source of NSCs that remains largely unexplored. Using single/dual-labeling procedures, we address the existence of NSCs in the innermost layers of the OB. In vivo, these cells are more quiescent that their SVZ counterparts, but after in vitro expansion, they behave similarly. Self-renewal and proliferation assays in co-culture with niche astrocytes indicate that OB-glia restricts NSC activity whereas SVZ-glia has the opposite effect. Gene expression profiling identifies WNT7A as a key SVZ-glial factor lac…
Goppa codes over Edwards curves
2023
Given an Edwards curve, we determine a basis for the Riemann-Roch space of any divisor whose support does not contain any of the two singular points. This basis allows us to compute a generating matrix for an algebraic-geometric Goppa code over the Edwards curve.
Deformation Quantization: Genesis, Developments and Metamorphoses
2002
We start with a short exposition of developments in physics and mathematics that preceded, formed the basis for, or accompanied, the birth of deformation quantization in the seventies. We indicate how the latter is at least a viable alternative, autonomous and conceptually more satisfactory, to conventional quantum mechanics and mention related questions, including covariance and star representations of Lie groups. We sketch Fedosov's geometric presentation, based on ideas coming from index theorems, which provided a beautiful frame for developing existence and classification of star-products on symplectic manifolds. We present Kontsevich's formality, a major metamorphosis of deformation qu…
Deformation quantization of covariant fields
2002
After sketching recent advances and subtleties in classical relativistically covariant field theories, we give in this short Note some indications as to how the deformation quantization approach can be used to solve or at least give a better understanding of their quantization.