Search

Description, Expression of miR-3607 in embryonic mammalian cerebral cortex was lost in rodents, limiting progenitor cell proliferation., The evolutionary expansion and folding of the mammalian cerebral cortex resulted from amplification of progenitor cells during embryonic development. This process was reversed in the rodent lineage after splitting from primates, leading to smaller and smooth brains. Genetic mechanisms underlying this secondary loss in rodent evolution remain unknown. We show that microRNA miR-3607 is expressed embryonically in the large cortex of primates and ferret, distant from the primate-rodent lineage, but not in mouse. Experimental expression of miR-3607 in embryonic mouse cortex led to increased Wnt/β-catenin signaling, amplification of radial glia cells (RGCs), and expansion of the ventricular zone (VZ), via blocking the β-catenin inhibitor APC (adenomatous polyposis coli). Accordingly, loss of endogenous miR-3607 in ferret reduced RGC proliferation, while overexpression in human cerebral organoids promoted VZ expansion. Our results identify a gene selected for secondary loss during mammalian evolution to limit RGC amplification and, potentially, cortex size in rodents.

Many different constitutive models that describe the behaviour of metal powder during hot isostatic processes are found in literature. A quantitative comparison of these material laws shows a huge discrepancy among the different existing models. This reveals the high sensitivity of the mechanical behaviour of porous materials to the shape, arrangement and distribution of particles and pores. In order to clarify these discrepancies, the compaction behaviour under high temperature hydrostatic loads for a Nickel-based superalloy has been experimentally characterized. In parallel, three different particle/pore configurations have been analysed at a mesoscopic scale by means of FEM using representative volume elements (RVEs) with periodic boundary conditions. The overall macroscopic response of each RVE has been obtained by a homogenization procedure. The results confirm the high sensitivity of the overall mechanical response to the microscopic arrangement of pores and particles.

The current COVID-19 pandemic has posed an unusual challenge to health services in all countries.

The microstructural and mechanical characterization of an equiatomic YGdTbDyHo high entropy alloy with hexagonal close-packed structure was performed. The phase state and chemical homogeneity of the solid solution were analysed with respect to crystal structure, phase stability, and oxide formation. It was found that Y-rich precipitates form at grain boundaries and that the alloy is prone to oxidation, leading to a homogeneous distribution of ∼10 nm-sized oxides in the grain interiors. The plastic response at the sub-grain level was studied in terms of the activated slip systems, critical resolved shear stresses (CRSS), and strain hardening using micropillar compression tests. We observe plastic slip on the basal system, with a CRSS of 196 ± 14.7 MPa. Particle strengthening and strength dependence on sample size are discussed on the basis of dislocation particle interaction and mechanical size effects.

El objetivo de este artículo es exponer y esclarecer conceptos básicos de los riesgos e incentivar, en los directivos y miembros de las empresas, el aprendizaje, específicamente, de los riesgos empresariales. De igual forma se ha realizado un análisis histórico lógico para llegar hasta la gestión de riesgos contemporánea. Cómo principales guías se toman los documentos normativos del control interno, las normas de la gestión de riesgos y la literatura especializada en este tema. El desconocimiento de esta temática hace que los planes de riesgos empresariales posean problemas conceptuales que perjudican la gestión y prevención de riesgos en las organizaciones. AbstractThe objective of this article is to expose and clarify basic concepts of risks and to encourage, in the managers and members of the companies, the learning, specifically, of the business risks. Likewise, a logical historical analysis has been carried out to reach contemporary risk management. The main guidelines are the normative documents of the internal control, the norms of the risk management and the literature specialized in this subject. The ignorance of this issue makes the business risk plans have conceptual problems that harm the management and prevention of risks in organizations.

En el presente artículo caracteriza el proceso de consultoría organizacional con la finalidad de proponer un modelo para sistematizarlo. Se aplica la metodología clúster y el análisis de clasificación por conglomerados jerárquicos por casos, para obtener, desde la perspectiva teórica las variables más representativas existentes en los modelos y procedimientos precedentes, con la asistencia del software IBM Statistical Package for the Social Sciences Statistics (SPSS), versión 21. En su conformación se utilizan técnicas cualitativas como la tormenta de ideas, encuesta y el trabajo en grupo.Como principal resultado se presenta un modelo conceptual para desarrollar los servicios de consultoría organizacional que se sustenta en los elementos esenciales más repetitivos e invariantes de los 21 modelos y procedimientos analizados, que integra las etapas generalmente aceptadas y las mejores prácticas del equipo consultor.El modelo propuesto, logra uniformidad al sistematizar la forma de desarrollar los servicios de consultoría, que se articula con el merco legal y está orientado al cliente, quedando constituido por cinco fases: concertación del servicio, exploración, planificación, ejecución e informe gerencial, entrega y conformación del expediente.

The micromechanical fracture behavior of Si [100] was investigated as a function of temperature in the scanning electron microscope with a nanoindenter. A gradual increase in KC was observed with temperature, in contrast to sharp transitions reported earlier for macro-Si. A transition in cracking mechanism via crack branching occurs at ∼300 °C accompanied by multiple load drops. This reveals that onset of small-scale plasticity plays an important role in the brittle-to-ductile transition of miniaturized Si.

La presente investigación está relacionada con la medición del grado de competencias que tienen los docentes de una Escuela de Ingeniería Financiera, con el fin de realizar un análisis de cumplimiento de acuerdo a las 16 competencias determinadas por el Concejo de Evaluación, Acreditación y Aseguramiento de la Calidad de la Educación Superior (CEAACES) del Ecuador. Para este análisis se utilizaron herramientas relacionadas con la lógica difusa y su objetivo fue conocer el estado general de las competencias de los docentes en la Escuela de Ingeniería en Finanzas, para diseñar una acertada estrategia de mejoramiento académico. Este artículo forma parte de una investigación realizada en una Facultad de Administración de Empresas, donde fueron evaluadas las cinco Escuelas que la conforman. AbstractThis research is related to the measurement of the degree of skills that teachers have a School Financial Engineering, in order to perform an analysis of compliance according to the 16 competencies identified by the Council of Evaluation, Accreditation and Quality Assurance in Higher Education (CEAACES) of Ecuador. For this analysis related to fuzzy logic and its objective was to determine the overall competence of teachers in the School of Engineering Finance to design a successful strategy Improvement tools they were used. This article is part of an investigation into a College of Business Administration, where they were evaluated the five schools that constitute it.

In hard coating development there is a need for fast and efficient screening methods to assess the influence of changes in composition and structure evolution on the mechanical behavior. Nanoindentation constitutes a method that allows fast and efficient probing of mechanical properties. For another important mechanical characteristic of hard coatings, the fracture toughness, no quick benchmark test to compare coatings with various compositions and/or morphologies, exist. Therefore, the goal of this investigation was to determine if a tensile test setup allows for fast and efficient qualitative screening of fracture toughness trends in hard coatings compared to accurate but time consuming micro-bending beam experiments. TiAlN and VAlN, each deposited on ductile Cu-substrates, were chosen for this investigation. In situ scanning electron microscopy tensile tests were performed. Here, the strain at crack initiation of the coating was utilized as the experimental parameter, which is most representative for the fracture toughness. The experiments indicate that TiAlN exhibits a higher fracture toughness than VAlN. This was confirmed using time demanding in situ micro-bending beam fracture experiments. Hence, it is established that under the given conditions macroscopic in situ SEM tensile tests can be used as a fast and efficient screening method for fracture toughness trends of hard coatings.

Materials and design 186, 108327 - (2020). doi:10.1016/j.matdes.2019.108327, High fracture toughness is crucial for the application of metallic glasses as structural materials to avoid catastrophicfailure of the material in a brittle manner. One fingerprint for fracture toughness in metallic glasses isthe fraction of hybridized bonds, which is affected by alloying Pd57.4Al23.5Y7.8M11.3 with M = Fe, Ni, Co, Cu, Os,Ir, Pt, and Au. It is shown that experimental fracture toughness data is correlated to the fraction of hybridizedbondswhich scalewith the localized bonds at the Fermi level. Thus, the localized bonds at the Fermi level are utilizedquantitatively as a measure for fracture toughness. Based on ab initio calculations, the minimum fraction ofhybridized bonds was identified for Pd57.4Al23.5Y7.8Ni11.3. According to the ansatz that the crystal orbital overlappopulation at the Fermi level scales with fracture toughness, for Pd57.4Al23.5Y7.8Ni11.3 a value of around 95 ±20 MPa·m0.5 is predicted quantitatively for the first time. Consistent with this prediction, in micro-mechanicalbeam bending experiments Pd57.4Al23.5Y7.8Ni11.3 thin films show pronounced plasticity and absence of crackgrowth., Published by Elsevier Science, Amsterdam [u.a.]

The design of multilayer stacks in the semiconductor industry requires knowledge of the delamination quantities. Previously, the determination of the mode-II failure has been problematic since the success-rate of current methods is low or the samples require superlayers that potentially alter the stack. We develop a method for mode-II testing that applies an additional normal force, which prevents mode-I opening and buckling. This method requires a nanoindenter with lateral force measurement capabilities and a FIB or lithographically structured sample. The experiments are fast, allowing for high-throughput testing. The method is applied to quantify the mode-II fracture of the Cu–SiO2 interface and we show the origins of the observed size-effect.

Transient liquid phase bonding offers one option to generate a robust lead-free die attach with sound thermal and electrical conductivity in microelectronic packages. However, it is a challenge to characterize the microstructure and mechanical behavior of the bonding layer because of its ultra-thin thickness and its nano-sized constituents. We show that microstructure s and local mechanical properties of such a modern solder systems are accessible with state-of-the-art methods including transmission electron microscope, synchrotron X-ray nano-beam diffraction as well as micro-scale mechanical testing. Three sub-regions with different morphologies have been identified within the bonding area, and their contained phases have been mapped. Two of the sub-regions contain nano-sized intermetallic compounds (IMC) while the third one is mostly composed of an FCC Au–Cu solid solution with a Cu concentration gradient. On top of that, micro-cantilever bending testing has been conducted to investigate the mechanical behavior of the bonding region. The two IMC sub-regions show brittle behavior while the Au–Cu sub-region is ductile.

El planteamiento de la empresa como sistema, dentro de la perspectiva económica y empresarial, es el objeto de estudio del presente trabajo donde realizamos una revisión de las distintas corrientes epistemológicas de la disciplina de la Economía de la Empresa. Se analiza su potencial carácter científico y la evolución histórica acontecida a partir de su especialización. La redefinición le proporciona esa dimensión sistémica (que la Economía general estaría perdiendo en sus formulaciones más teóricas y puristas) que le permitiría captar toda la complejidad relacional de la empresa y posibilitar su percepción como una realidad inmersa en el cambio y la continuidad. De ese modo, la teoría general de sistemas, entendida como método transdisciplinario, parece constituirse como el marco más adecuado para el estudio de la empresa, siguiendo el denominado enfoque sistémico. This paper reviews the origin and history of the thinking of the enterprise or firm as a system, studying the different epistemological currents of the discipline of Business and Economics, with the main purpose being the consideration of the discipline of Business Administration from a Systems Science approach. This revisioning or redefinition engaging the systemic dimension enables one to capture all the relational complexity of the company and its conceptualization as a reality steeped in change and continuity. Therefore, general systems theory, understood as a transdisciplinary approach, seems to be the most appropriate framework for the study of the company, following the so-called systemic approach.

En el marco del Proyecto Prometeo, la Escuela Superior Politécnica de Chimborazo (ESPOCH) inicia la implementación del Balanced Scorecard (BSC) o Cuadro de Mando Integral, como modelo de Gestión Universitaria. El objetivo principal de esta investigación es implementar en la ESPOCH, el BSC como Modelo de Gestión y establecer Cuadros de Mando para sus Subsistemas y Facultades. Para el desarrollo del trabajo se tuvo en cuenta las teorías de Robert Kaplan y David Norton respecto al BSC, la utilización del Cuadro de Mando ODUN, además, de utilizar métodos comparativos y de análisis con otras experiencias en la gestión universitaria. Finalmente se implementó el BSC que facilitó el Control de Gestión en la ESPOCH.Palabras Clave: Balanced Scorecard, Sistema de Gestión de la Calidad, Cuadro de Mando. Within the Prometeo Project, the Escuela Superior Politécnica de Chimborazo (ESPOCH) started implementing the Balanced Scorecard (BSC) as a model of University Management. The objectives of this project are to implement BSC in the ESPOCH, in its five subsystems and seven faculties. In order to develop of the research, we considered the theories of Robert Kaplan and David Norton and the use of the dashboard ODUN. A comparative analysis with other university management methods was carried out. Finally, the BSC was implemented; this benefitted the operational management of ESPOCH.

The domes studied, widespread in a large area of the Mediterranean, constitute an architectural heritage of great value to the history of architecture and construction. They were all built using brick masonry and ceramic tile roofs. Restoration work has made it possible to define their geometry, including the construction layouts of the buildings. In addition, on inspection it can be seen that common construction problems tend to be located at specific critical points. The restoration process of different cases sharing the same methodology, construction criteria, and solutions is accurately described. Following international charters, there is minimal intervention and maximum respect for the original solutions, but also a carefully considered incorporation of new materials and technologies to improve the critical points.

Compression tests of 〈1 1 1〉-oriented LiF single-crystal micropillars 1–5 μm in diameter were carried out from 25 °C to 250 °C. While the flow stress at ambient temperature was independent of the micropillar diameter, a strong size effect developed with elevated temperature. This behavior was explained by rigorously accounting for the different contributions to the flow stress of the micropillars as a function of temperature and pillar diameter: the lattice resistance, the forest hardening; and the size-dependent contribution as a result of the operation of single-arm dislocation sources. This was possible because the micropillars were obtained by chemically etching away the surrounding matrix in directionally solidified LiF–NaCl and LiF–KCl eutectics, avoiding any use of focused ion beam methods, yielding micropillars with a controlled dislocation density, independent of the sample preparation technique. In particular, the role of the lattice resistance on the size effect of micrometer-size single crystals was demonstrated unambiguously for the first time. This result rationalizes the different values of power-law exponent for the size effect found in the literature for face-centered cubic and body-centered cubic metals as well as for covalent and ionic solids.

Galiellalactone (GL) is a metabolite produced by the fungus Galiella rufa that presents antitumor and immunomodulatory activities. GL interferes with the binding to DNA of signal transducer and activator of transcription (STAT)-3 and also inhibits other signal pathways such as NF-κB, but the mechanism of action in this pathway remains unknown. In this study we report that GL inhibits vesicular stomatitis virus-recombinant HIV-1 infection and the NF-κB-dependent transcriptional activity of the HIV-LTR promoter. We found that GL prevents the binding of NF-κB to DNA but neither affects the phosphorylation and degradation of NF-κB inhibitory protein, IκBα, nor the phosphorylation and acetylation of the NF-κB p65 subunit. However, GL prevents the association of p65 with the importin α3 impairing the nuclear translocation of this transcription factor. Using a biotinylated probe we found that GL binds to p65 but not to importin α3. Therefore, GL is a dual NF-κB/STAT3 inhibitor that could serve as a lead compound for the development of novel drugs against HIV-1, cancer and inflammatory diseases.

Porous and nanoporous aluminum have been fabricated via selective dissolution. Al-Zn alloys were dealloyed in an aqueous solution of nitric acid to selectively dissolve zinc. Fast solidification methods permitted to adjust the precursor microstructure of the parent alloy in order to induce supersaturation of zinc in aluminum. An electric potential applied during corrosion affected the final morphology of porosity. Electronic imaging evinced the presence of regions with less than 100 nm diameter pores. This nanoporosity was only present in electrochemically dealloyed samples. We observed two types of porosity in dealloyed samples: a primary porosity resulting from the selective removal of zinc-rich interdendritic phases and a secondary porosity resulting from nanoporosity evolution inside zinc-supersaturated dendrites.

Sentinel lymph node (SLN) biopsy is the standard of practice for assessing axillary spread in clinically node-negative breast cancer patients. On the other hand, axillary lymph node dissection (ALND) is the ideal procedure for patients with SLN metastasis. Different studies over the last few years have suggested that some patients with positive SLN can be treated without ALND. This article presents a literature review carried out by our multidisciplinary group and its strategy for avoiding routine ALND in women with SLN metastases. In this new strategy ALND should not be performed on women with T1 tumours, with 1-2 positive SLN and undergoing breast conservative surgery. On the other hand, ALND would be indicated in those patients with three or more positive SLN, presence of extracapsular invasion, mastectomised women and triple negative subtype or HER2+ tumours that have not received biological treatment with antibodies.

The effect of crystal misorientation, geometrical tilt, and contact misalignment on the compression of highly anisotropic single crystal micropillars was assessed by means of crystal plasticity finite element simulations. The investigation was focused in single crystals with the NaCl structure, like MgO or LiF, which present a marked plastic anisotropy as a result of the large difference in the critical resolved shear stress between the “soft” {110}〈110〉 and the “hard” {100}〈110〉 active slip systems. It was found that contact misalignment led to a large reduction in the initial stiffness of the micropillar in crystals oriented in the soft and hard direction. The crystallographic tilt did not modify, however, the initial crystal stiffness. From the viewpoint of the plastic response, none of the effects analyzed led to significant differences in the flow stress when the single crystals were oriented along the “soft” [100] direction. Large differences were found, however, if the single crystal was oriented in the “hard” [111] direction as a result of the activation of the soft slip system. Numerical simulations were in very good agreement with experimental literature data.

Coupling reactions of CO2 and epoxides to produce either cyclic carbonates or polycarbonates are environmentally friendly reactions that allow the use of an inexpensive and renewable feedstock while achieving carbon efficiency. In this study, density functional theory calculations were used to understand the role the metal(salen) catalyst on CO2 adsorption. We have performed a systematic analysis of the plausible interactions of CO2 with metal(salen) catalysts and ethylene oxide/metal(salen) complexes. Adsorption reactions were analyzed on six metal(salen) complexes: Co, Cr, Mn, Fe, Zn, and Al, using the unrestricted OPBE functional. Geometry optimizations were carried out beginning with a variety of different conformations and frequency calculations were used to verify that structures lie in an energy minimum. Our results demonstrate that CO2 does not bind to the metal atom of the bare metal(salen). The adsorption of CO2 onto metal(salen) complexes is an endothermic reaction and the lowest energy adsorbed complex involves the interaction of CO2 with the adsorbed opened-epoxide.

[ESP] Se presenta en este artículo el estudio de las dos bóvedas de arcos entrecruzados existentes en la torre del homenaje del castillo de la Atalaya de Villena. La parte inferior de esta torre corresponde, con bastante probabilidad, a una obra almohade de finales del s. XII hecha de tapia de hormigón de cal y cuyas dos salas interiores se cubren con bóvedas de nervios entrecruzados construidos con ladrillo. La geometría y trazado de las bóvedas y sus nervaduras pertenecen claramente a la tradición de este tipo de abovedamientos característico de la arquitectura andalusí. La investigación se apoya en una metodología que interrelaciona: un preciso levantamiento geométrico, las lecturas estratigráficas, la definición de técnicas constructivas y la toma de muestras para la datación y caracterización de los materiales empleados. La principal aportación del artículo es la propuesta metodológica que plantea la necesidad del estudio del sistema constructivo y del proceso seguido en su ejecución, de una tipología basada principalmente en aspectos morfológicos, pero insuficientemente valorada respecto a su singularidad constructiva. [ENG] This paper deals with the study of the two vaults with intercrossed arches of the keep of Atalaya castle of Villena (Spain). The lower part of the tower corresponds, quite possibly, with the Almohad phase, of the late 12th century. It is built with thick tapia walls, whose two interior rooms are covered with vaults with brick intercrossed arches. The geometry and tracing of the vaults and ribs belong to the tradition of this type of vaulting, characteristic of andalusí architecture. The research is based on a methodology that interrelates: precise geometric survey, stratigraphic readings, definition of construction techniques and collection of samples for dating and characterization of the materials used. The main contribution of this paper is the methodology that raises the need to study the construction system and the process followed in the execution, of a typology based primarily on morphological aspects, but undervalued in relation with the constructive features

In this work, the nanostructure of a Mo2BC hard coating was determined by several transmission electron microscopy methods and correlated with the mechanical properties. The coating was deposited on a Si (100) wafer by bipolar pulsed direct current magnetron sputtering from a Mo2BC compound target in Ar at a substrate temperature of 630 °C. Transmission electron microscopy investigations revealed structural features at various length scales: bundles (30 nm to networks of several micrometers) consisting of columnar grains (∼10 nm in diameter), grain boundary regions with a less ordered atomic arrangement, and defects including disordered clusters (∼1.5 nm in diameter) as well as stacking faults within the grains. The most prominent defect with a volume fraction of ∼0.5% is the disordered clusters, which were investigated in detail by electron energy loss spectroscopy and atom probe tomography. The results provide conclusive evidence that Ar is incorporated into the Mo2BC film as disordered Ar-rich Mo-B-C c...

N-Arachidonoylphenolamine (AM404), a paracetamol lipid metabolite, is a modulator of the endocannabinoid system endowed with pleiotropic activities. AM404 is a dual agonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1) and the Cannabinoid Receptor type 1 (CB₁) and inhibits anandamide (AEA) transport and degradation. In addition, it has been shown that AM404 also exerts biological activities through TRPV1- and CB₁ -independent pathways. In the present study we have investigated the effect of AM404 in the NFAT and NF-κB signaling pathways in SK-N-SH neuroblastoma cells. AM404 inhibited NFAT transcriptional activity through a CB₁- and TRPV1-independent mechanism. Moreover, AM404 inhibited both the expression of COX-2 at transcriptional and post-transcriptional levels and the synthesis of PGE₂. AM404 also inhibited NF-κB activation induced by PMA/Ionomycin in SK-N-SH cells by targeting IKKβ phosphorylation and activation. We found that Cot/Tlp-2 induced NFAT and COX-2 transcriptional activities were inhibited by AM404. NFAT inhibition paralleled with the ability of AM404 to inhibit MMP-1, -3 and -7 expression, cell migration and invasion in a cell-type specific dependent manner. Taken together, these data reveal that paracetamol, the precursor of AM404, can be explored not only as an antipyretic and painkiller drug but also as a co-adjuvant therapy in inflammatory and cancer diseases.

The N-acyl conjugates of amino acids and neurotransmitters (NAANs) are a class of endogenous lipid messengers that are expressed in the mammalian central and peripheral nervous system. Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that plays a key role in the cellular adaptation to hypoxia and ischemia, and hypoxic preconditioning through HIF-1α has been shown to be neuroprotective in ischemic models. This study showed that N-acyl-dopamines induce HIF-1α stabilization on human primary astrocytes and neurons as well as in transformed cell lines. N-arachidonoyl-dopamine (NADA)-induced HIF-1α stabilization depends on the dopamine moiety of the molecule and is independent of cannabinoid receptor-1 (CB1) and transient receptor potential vanilloid type I (TRPV1) activation. NADA increases the activity of the E3 ubiquitin ligase seven in absentia homolog-2 (SIAH2), inhibits prolyl-hydroxylase-3 (PHD3) and stabilizes HIF-1α. NADA enhances angiogenesis in endothelial vascular cells and promotes the expression of genes such as erythropoietin (EPO), vascular endothelial growth factor A (VEGFA), heme oxygenase 1 (HMOX-1), hexokinase 2 (HK2) and Bcl-2/E1B-nineteen kiloDalton interacting protein (BNIP3) in primary astrocytes. These findings indicate a link between N-acyl-dopamines and hypoxic preconditioning and suggest that modulation of the N-acyl-dopamine metabolism might prove useful for prevention against hypoxic diseases.

Sentinel lymph node (SLN) biopsy is the standard of practice for assessing axillary spread in clinically node-negative breast cancer patients. On the other hand, axillary lymph node dissection (ALND) is the ideal procedure for patients with SLN metastasis. Different studies over the last few years have suggested that some patients with positive SLN can be treated without ALND. This article presents a literature review carried out by our multidisciplinary group and its strategy for avoiding routine ALND in women with SLN metastases. In this new strategy ALND should not be performed on women with T1 tumours, with 1-2 positive SLN and undergoing breast conservative surgery. On the other hand, ALND would be indicated in those patients with three or more positive SLN, presence of extracapsular invasion, mastectomised women and triple negative subtype or HER2+ tumours that have not received biological treatment with antibodies.