Reactive Palladium Carbenes: Migratory Insertion and Other Carbene-Hydrocarbyl Coupling Reactions on Well-Defined Systems

Producción CientíficaPalladium complexes with carbene ligands are among the best known and more extensively used catalysts. Those carbenes are usually NHC or N,N-disubstituted derivatives and their use relies on the robust nature of the carbene ligands and their role as auxiliary ligands that modify the metal's elec- tronic and steric features. In contrast, there are other types of carbenes that, when coordinated to palladium, lead to transfor- mations in which the carbene fragment is involved. In the last decade, palladium-catalyzed reactions have been extended to the use of carbene precursors that can be functionalized with the formation of several C–C bonds in one reaction step. Plausi- ble mechanisms have been proposed where a carbene–hydro- carbyl coupling occurs in the palladium coordination sphere. This microreview aims to collect and discuss the examples of organometallic reactions in well-characterized palladium com- plexes where the carbene is one of the fragments involved in C–C bond formation. These examples are key in understanding and supporting the mechanisms proposed for the Pd-catalyzed of C–C coupling reactions of carbenes.MINECO (SGPI, grant CTQ2016-80913-P)Junta de Castilla y León (grants VA062G18 and VA051P17

Vinylic Addition Polynorbornene in Catalysis

Vinylic addition polynorbornenes (VA-PNB) result from the insertion polymerization of norbornene or specific norbornene derivatives catalyzed by transition metal com- plexes. The VA-PNB skeleton is completely aliphatic and keeps the bicyclic structure of norbornene. This saturated polymer is thermally and chemically very stable and it is a very robust scaffold to support catalysts or reagents for catalytic applications. Several VA-PNBs are now available with suitable functional groups (halogen, alkenyl, carbonates) that can be used as starting materials to introduce the functionalization of choice by post-polymerization reactions. This has been applied to anchor organocatalysts on VA-PNB as well as ligands that can be used to synthesize supported metal catalysts. The reported examples of the use of VA-PNB-linked catalysts and their recyclability will be presented. VA-PNBs have also proved useful in the context of organotin chemistry to solve the problem of tin contamination by an efficient separation and the reuse of tin byproducts. Its uses in the Stille cross-coupling reaction and tin-hydride radical proc- esses will be discussed.MINECO (SGPI, grant CTQ2016-80913-P)Junta de Castilla y León (grants VA062G18 and VA051P17 and a fellowship to RGL

Dynamic price competition with fixed capacities

Many revenue management (RM) industries are characterized by (a) fixed capacities in the short term (e.g., hotel rooms, seats on an airline flight), (b) homogeneous products (e.g., two airline flights between the same cities at similar times), and (c) customer purchasing decisions largely influenced by price. Competition in these industries is also very high even with just two or three direct competitors in a market. However, RM competition is not well understood and practically all known implementations of RM software and most published models of RM do not explicitly model competition. For this reason, there has been considerable recent interest and research activity to understand RM competition. In this paper we study price competition for an oligopoly in a dynamic setting, where each of the sellers has a fixed number of units available for sale over a fixed number of periods. Demand is stochastic, and depending on how it evolves, sellers may change their prices at any time. This reflects the fact that firms constantly, and almost costlessly, change their prices (alternately, allocations at a price in quantity-based RM), reacting either to updates in their estimates of market demand, competitor prices, or inventory levels. We first prove existence of a unique subgame-perfect equilibrium for a duopoly. In equilibrium, in each state sellers engage in Bertrand competition, so that the seller with the lowest reservation value ends up selling a unit at a price that is equal to the equilibrium reservation value of the competitor. This structure hence extends the marginal-value concept of bid-price control, used in many RM implementations, to a competitive model. In addition, we show that the seller with the lowest capacity sells all its units first. Furthermore, we extend the results transparently to n firms and perform a number of numerical comparative statics exploiting the uniqueness of the subgame-perfect equilibrium.revenue management, bid-prices, subgame-perfect equilibrium.

[2,2′-Bipyridin]-6(1H)-one, a Truly Cooperating Ligand in the Palladium-Mediated C–H Activation Step: Experimental Evidence in the Direct C-3 Arylation of Pyridine

Producción CientíficaThe ligand [2,2′-bipyridin]-6(1H)-one (bipy-6-OH) has a strong accelerating effect on the Pd- catalyzed direct arylation of pyridine or arenes. The isolation of relevant intermediates and the study of their decomposition unequivocally show that the deprotonated coordinated ligand acts as a base and assists the cleavage of the C−H bond. Mechanistic work indicates that the direct arylation of pyridine with this ligand occurs through a Pd(0)/Pd(II) cycle. Because of this dual ligand− intramolecular base role, there is no need for an available coordination site on the metal for an external base, a difficulty encountered when chelating ligands are used in coupling reactions that involve a C−H cleavage step.MINECO (SGPI, grant CTQ2016-80913-P, BES-2014- 067770 fellowship to A.T.)Junta de Castilla y Leoń (grants VA062G18 and VA051P17)Universidad de Valladolid (fellowship to V.S.)

La educación secundaria en Navarra en el siglo XIX

L'Educació Secundària a Navarra al Segle XIX L'autora explica els inicis de l'ensenyament secundari a la comunitat navarresa -Tudela, Estella, Tafalla...-, i d'una manera aprofundida, en la creació i desenvolupament de l'Institut provincial de Pamplona. Al llarg de l'article descriu moments importants d'aquesta evolució, com l'aprovació del Pla General d'Instrucció Pública el 1845 i el paper que hi va tenir la Junta Inspectora, així com també es menciona la promulgació de la Llei Moyano, l'oferta d'altres opcions post-obligatòries, la implantació de diferents plans d'estudi, realitats polítiques d'aquell període... L'establiment del precepte de realitzar memòries anuals en aquella època ha permès als historiadors conèixer fets i detalls valuosos sobre els canvis que s'anaven produint i sobre dades concretes referides a nombre d'alumnat, dotacions econòmiques, etc. A partir del darrer terç del segle passat es produí un augment de l'escolarització d'alumnes en centres privats religiosos en detriment de l'ensenyament oficial.Secondary Education in Navarra in the XIX century The author explains the beginnings of secondary education in the community of Navarra -Tudela, Estella, Tafalla...-, and gives an in-depth look at the creation and development of the Pamplona provincial institute. Throughout the article she describes such important events in this evolution as the approval of the General Public Instruction Plan of 1845 and the role that the Board of Inspectors played, or the announcement of the Moyano Law and its effects, the offer of other post obligatory options, the implantation of different study plans, political realities of the period... The establishment of the setting up of annual reports during that era has helped historians to discover valuable facts and details about the changes that were occuring and about concrete information with reference to the number of students, economic background, etc. From about the final third of the last century the number of students in private religious centre rose in detriment to the number in official education

Mechanisms of invasion and metastasis in colorectal cancer

[spa] Parte de esta investigación consiste en explorar los mecanismos involucrados en el patrón metastático de CCR. Asimismo usamos datos epidemiológicos donde evaluamos la asociación entre el polimorfismo intrónico de SMAD7 (rs4939827, 18q21) con el genotipo y características tumorales. En el primer proyecto usamos un modelo murino de metástasis hepáticas para crear un derivado celular con alto tropismo metastático a hígado y pulmón. Mediante análisis de expresión de genes usando chips de transcripción identificamos 194 genes diferencialmente expresados El análisis de muestras clínicas mostró que aquellos pacientes cuyo tumor presentaba bajos niveles de p38 sufrían una mayor frecuencia de metástasis al pulmón, pero no a otros órganos. Al tratar ratones que habían desarrollado metástasis hepáticas derivadas de la línea celular parental con un inhibidor específico de p38, vimos que se incrementaba la afinidad metastática al pulmón. Evidenciamos que p38, a través del silenciamiento de PTHLH, en el derivado celular altamente metastático disminuía su capacidad de colonizar el pulmón. Demostramos que PTHLH induce la apoptosis de células humanas de endotelio pulmonar a través del factor AIFM1, facilitando que las células metastáticas puedan extravasarse al pulmón. En el segundo proyecto evaluamos la asociación de un polimorfismo intrónico del gen SMAD7 con el fenotipo y varias características moleculares del tumor. Para ello empleamos 1509 casos de cáncer de colon y recto y 2307 controles emparejados anidados en las cohortes Nurses Health Study y Health Professionals Follow-up Study. Encontramos que el alelo de menor frecuencia de rs4939827 (G) se asociaba con un menor riesgo de desarrollar un CCR con un estadio pT1 o pT2 [razón de odds (OR) ajustada, 0.73; intervalo de confianza al 95\% (CI) 0.62-0.87] pero no con tumores con estadio pT3 o pT4 (OR ajustada, 1.07; 95\% CI 0.93-1.23, valor p de heterogeneidad = 1.2 x 10-4). La asociación entre el polimorfismo de rs4939827 y CCR también difería significativamente según la metilación de RUNX3 (valor p de heterogeneidad = 0.005). Entre aquellos pacientes diagnosticados con CCR, el alelo de menor frecuencia de rs4939827 (G) estaba significativamente asociado con peor supervivencia (hazards ratio, 1.20; 95\% CI, 1.02-1.42).[eng] We studied the mechanisms driving the metastatic spread in colorectal cancer (CRC), focusing in the MAPK pathway. We developed in vivo a highly metastatic cell line using a KRAS-mutated cell line (SW620) in an ortothopic xenograft mouse model and used both in vivo and in vitro experiments to evaluate the mechanisms of metastasis. We also used data from two large prospective cohorts of incident CRC to evaluate the association of an intronic variant of SMAD7 (rs4939827, 18q21) with the phenotype and molecular characterisitics of CRC. In the first project, we inoculated SW620 luciferase-expressing cells into portal circulation of immunodeficient mice via intrasplenic injection followed by splenectomy, in order to isolate cell populations that target the liver. Comparative transcriptomic analysis identified 194 genes differentially expressed between the parental and the highly metastatic cell line. We found pathways of nitrogen metabolism, cell adhesion molecules and mitogen-activated protein kinases (MAPKs). Downregulation of ERK2 (but not of ERK1) in the highly metastatic cell line reverted its metastatic capacity to the liver, but not to the lung in our mice model. We thus hypothesized that the ability to metastasize the lung by the highly metastatic derivative had to be driven by other mechanism. The expression of parathyroid hormone-like hormone (PTHLH) was upregulated in our highly metastatic derivative and was inversely correlated with the expression of MKK6. Downregulation of PHTLH in the highly metastatic derivative decreased its capacity to colonize the lung without decreasing its capacity to colonize the liver after intra portal inoculation. We evidenced that PTHLH induced apoptosis of human pulmonary endothelial cells via apoptosis-inducing factor mitochondrion-associated 1. In the second project we evaluated the association of the SMAD7 intronic variant with tumor phenotype and several CRC molecular characteristics. We used 1509 CRC cases and 2307 age-matched controls nested within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). We randomly selected between one and three matched controls. Among the 1509 cases with blood or buccal samples in this study, we were able to successfully obtain tissue suitable for molecular analyses in 658 cases. We genotyped rs4939827 (TaqMan) successfully in 98% of the samples in NHS and 99.6% of the samples in HPFS. The phenotipic features evaluated were: TNM stage, grade of differentiation, location of the primary tumor (colon vs. rectum) and age at diagnosis. The evaluated molecular characteristics were DNA methylation of RUNX3 and LINE-1 (long interspersed nucleotide element-1), CpG island methylator phenotype (CIMP), microsatellite instability, TP53 expression by immunohistochemistry and the mutational status of BRAF, KRAS and PIK3CA. We found that the minor allele (G) in rs4939827 was associated with a lower risk of developing tumor stage pT1 or pT2 CRC [multivariate odds ratio (OR), 0.73; 95% confidence interval (CI) 0.62-0.87] but not tumor stage pT3 or pT4 (multivariate OR, 1.07; 95% CI 0.93-1.23, P for heterogeneity = 1.2 x 10-4). The association between rs4939827 and CRC also significantly differed by methylation of RUNX3 (P for heterogeneity = 0.005). Among those with CRC, the minor allele (G) in rs4939827 was significantly associated with poorer overall survival (hazards ratio, 1.20; 95% CI, 1.02-1.42). In conclusion, we provide clinical and molecular evidence showing that ERK2 activation provides colon cancer cells with the ability to seed and colonize the liver and reduced p38 MAPK signalling endows cancer cells with the ability to form lung metastasis from previously established liver lesions. We also show that patients with the rs4939827 CRC-susceptibility locus diagnosed with CRC tend to develop tumors with greater invasiveness (as measured by the pT stage)

El tamaño importa. Política multiescalar en entornos post-humanos

The article approaches politics as an eminently controversial and multiscalar phenomenon. It reviews different versions of politics that coexist in post-human settings, not necessarily in an harmonious or complementary way. These range from the conventional forms or terminals of politics (megalopolitics), in which the awareness that one is practicing politics and the practice of politics are coincidental aspects, to other more complex articulations in which the political is more structuring in its effects where it is less recognisabel as experience. To make these new articulations intelligible - or which biopolitics or the politics of bodies, and nanopolitics or the politics of (all) things are the most outstanding - it is necessary to elaborate new conceptual ensembles that disfigure politics, which until now has been caught in the figurative trap of anthropocentrism.El artículo aborda la política como un fenómeno eminentemente controvertido y multiescalar. En él se hace un repaso de distintas versiones de la política que coexisten en entornos post-humanos, pero no de manera necesariamente armoniosa o complementaria: desde las formas convencionales o terminales de la política (la megalopolítica) en las que saberse haciendo política y hacer política son aspectos coincidentes, a otras articulaciones más complejas en las que lo político es más estructurante allí donde es menos reconocible como experiencia. Para hacer inteligibles estas nuevas articulaciones, de entre las que destacan la biopolítica o política de los cuerpos, y la nanopolítica o política de (todas) las cosas, es preciso elaborar nuevos dispositivos que desfiguren una política hasta ahora presa de la trampa figurativa del antropocentrismo

Bruno Latour: Politics of nature. How to bring the sciences into democracy. Harvard University Press, Cambridge, 2004

Sin resume

Significados personales de la derivada en estudiantes de ingeniería

Esta investigación se centra en la caracterización de los significados personales de la derivada en estudiantes de Ingeniería y se desarrolla considerando diferentes dificultades que surgen en el proceso de enseñanza y aprendizaje de las derivadas. El marco teórico se fundamenta en la adopción del modelo semiótico-antropológico propuesto por Godino y Batanero (1994) y utilizado por Arrieche (2002), entre otros. Se establecen y estudian las tres facetas que deben ser consideradas en un proyecto de investigación en Didáctica de la Matemática: epistemológica, cognitiva e instruccional. Metodológicamente, se combinan enfoques cualitativos en las fases epistemológica e instruccional con esquemas cuantitativos en la fase cognitiva. Mediante el análisis semiótico se evalúan los resultados