Theoretical insights into the E1cB/E2 mechanistic dichotomy of elimination reactions

E1cB and E2 eliminations have been described as competing mechanisms that can even share a common pathway when the E1cB/E2 borderline mechanism operates. A suitable case study evincing such a mechanistic dichotomy corresponds to the elimination reaction of β-phenylmercaptoethyl phenolate, since its mechanism has been thought to be an E2 elimination. Nonetheless, according to the computational assessment of the substituents on the leaving group, we demonstrate that the reaction proceeds via a borderline E1cB mechanism. Stabilization of the carbanion was provided not only by substituent effects tuning the nucleofugality of the leaving group, but also by a base, since distortion/interaction–activation strain and Natural Bond Order (NBO) analyses suggest a stabilizing interaction between the base and C_β of the E1cB intermediate. In order to gain insights into these results in a more general context, we have rationalized them with a qualitative picture of the E1cB/E2 mechanistic dichotomy using simple relationships between diabatic parabolas modeling the potential wells of reactants, intermediates, and products. In this Diabatic Model of Intermediate Stabilization (DMIS), the borderline E1cB mechanism for the elimination reaction of β-phenylmercaptoethyl phenolate was discussed in terms of bonding and dynamic stepwise processes. The conceptual model presented herein should be useful for the analysis of any reaction comprising competing one- and two-step mechanisms

Sistema integrado para toma de decisiones en el diseño de estructuras de hormigón

This paper presents a methodology to analyze decisions in the design of concrete structures. Specifically, we propose a multi-criteria approach to assess the value implications of precast concrete technologies versus in-situ concrete solutions. First, we emphasize the importance of careful decision-making in early stages of construction projects to enhance customer value. Second, we present a decisionmaking methodology that uses fuzzy logic to represent and synthesize information about risk-return tradeoffs in the different kinds of variables involved in the evaluation of a project’s value. To illustrate, we use our methodology to analyze precast vs. in-situ solutions in the design of drainage structures. The results of our analysis point at precast solutions as the most desirable design choice in this setting, and highlight the importance of value analysis in early stages of construction projects.El presente artículo hace una breve reflexión sobre las alternativas in situ y prefabricadas para estructuras de hormigón, justificando la necesidad de profundizar en métodos multicriterio como ayuda a la toma de decisiones. Manifiesta la trascendencia de la calidad en las decisiones más allá de este ámbito concreto, así como su influencia en la mayor eficiencia de las obras. Presenta luego un sistema de ayuda a la toma de decisiones basado en matemática difusa, que considera el valor de cada alternativa contemplando el riesgo inherente. Para ilustrarlo desarrolla un ejemplo aplicado a pasos inferiores que pueden resolverse mediante prefabricación o in situ. Efectuándolo por completo, llega a dos conclusiones principales: la bondad de la herramienta presentada y cómo la solución prefabricada, en este caso, aporta mayor valor. Concluye también que todo buen gestor debe plantearse su toma de decisión desde los inicios de cualquier proyecto, empleando herramientas como la presentada

Meisenheimer complexes as hidden intermediates in the aza-S_NAr mechanism

In this work we report a computational study about the aza-S_NAr mechanism in fluorine- and chlorine-containing azines with the aim to unravel the physical factors that determine the reactivity patterns in these heterocycles towards propylamine. The nature of the reaction intermediate was analyzed in terms of its electronic structure based on a topological analysis framework in some non-stationary points along the reaction coordinate. The mechanistic dichotomy of a concerted or a stepwise pathway is interpreted in terms of the qualitative Diabatic Model of Intermediate Stabilization (DMIS) approach, providing a general mechanistic picture for the S_NAr process involving both activated benzenes and nitrogen-containing heterocycles. With the information collected, a unified vision of the Meisenheimer complexes as transition state, hidden intermediate or real intermediate was proposed

Meisenheimer complexes as hidden intermediates in the aza-S_NAr mechanism

In this work we report a computational study about the aza-S_NAr mechanism in fluorine- and chlorine-containing azines with the aim to unravel the physical factors that determine the reactivity patterns in these heterocycles towards propylamine. The nature of the reaction intermediate was analyzed in terms of its electronic structure based on a topological analysis framework in some non-stationary points along the reaction coordinate. The mechanistic dichotomy of a concerted or a stepwise pathway is interpreted in terms of the qualitative Diabatic Model of Intermediate Stabilization (DMIS) approach, providing a general mechanistic picture for the S_NAr process involving both activated benzenes and nitrogen-containing heterocycles. With the information collected, a unified vision of the Meisenheimer complexes as transition state, hidden intermediate or real intermediate was proposed

Undetectable Levels of CSF Amyloid-β Peptide in a Patient with 17β-Hydroxysteroid Dehydrogenase Deficiency

17β-hydroxysteroid dehydrogenase 10 (HSD10) deficiency is a rare X-linked inborn error of isoleucine catabolism. Although this protein has been genetically implicated in Alzheimer's disease pathogenesis, studies of amyloid-β peptide (Aβ) in patients with HSD10 deficiency have not been previously reported. We found, in a severely affected child with HSD10 deficiency, undetectable levels of Aβ in the cerebrospinal fluid, together with low expression of brain-derived neurotrophic factor, α-synuclein, and serotonin metabolites. Confirmation of these findings in other patients would help elucidating mechanisms of synaptic dysfunction in this disease, and highlight the role of Aβ in both early and late periods of life

Ampliación del área de distribución de <i>Liolaemus carlosgarini</i> (Esquerré, Núñez & Scolaro, 2013) en la Reserva Nacional Altos de Lircay (Chile)

República de Chile, VII Región del Maule, Provincia de Talca, Reserva Nacional Altos de Lircay, sendero Laguna del Alto (35°36’4,12’’S; 71°00’19,01’’O. WGS84. 2023 m s.n.m.). Los ejemplares se recolectaron el 30 de enero de 2014. Fueron colectados por Gabriel Ormazábal, Gustavo Escobar Huerta, Juan Carlos Ortiz y Romina Carvajal. El material fue verificado por Pedro Victorianio y depositado en la colección herpetológica del Museo de Zoología de la Universidad de Concepción, Chile (MZUC). Se capturaron dos ejemplares, una hembra adulta (MZUC 41205) y una hembra juvenil (MZUC 41206).Facultad de Ciencias Naturales y Muse

Cortactin (CTTN) overexpression in osteosarcoma correlates with advanced stage and reduced survival

The cortactin (CTTN) gene has been found, by transcriptomic profiling, to be overexpressed in pediatric osteosarcoma. The location of CTTN at 11q13 and the role of cortactin in cytoskeleton restructuring make CTTN of interest as a potential biomarker for osteosarcoma. MATERIALS AND METHODS: Osteoblasts were isolated from 20 high-grade osteosarcomas before chemotherapy, and paired with cell samples from normal tissue, prior to RNA expression analysis on HG-U133A chips (Affymetrix). Semiquantitative CTTN mRNA expression was analyzed by real-time PCR. An osteosarcoma tissue microarray (TMA) containing 233 tissue spots from 48 patients was used for an immunohistochemical (IHC) study of cortactin. RESULTS: Transcriptomic profiling and real-time PCR analysis indicated increased CTTN expression in osteosarcomas (p = 0.001, Student's T test). TMA IHC showed cortactin to be present more frequently and in greater abundance in osteosarcomas than non-tumoral osteoblastic samples (p< 0.006, Mann-Withney test). Analysis of clinical outcomes indicated that overall survival for patients with primary tumors positive for cortactin was significantly lower than that for patients with cortactin negative (or only weakly staining) tumors (p = 0.0278, Log-rank test). CONCLUSIONS: Our preliminary data support the hypothesis that over-expression of cortactin, contained in the 11q13 amplicon, is involved in osteosarcoma carcinogenesis. The potential of cortactin overexpression as a biomarker for osteosarcoma is consolidated