Magnetic resonance imaging based signal intensity mapping predicts appropriate therapies after prophylactic ventricular tachycardia substrate ablation in patients with previous myocardial infarction and secondary prevention implantable cardioverter-defibrillator implantation

The aim of this study was to determine the capability of ceMRI based signal intensity (SI) mapping to predict appropriate ICD therapies after PVTSA.

Assessment of the influence of the elastic properties of rail vehicle suspensions on safety, ride quality and track fatigue

A sensitivity analysis has been performed to assess the influence of the elastic properties of railway vehicle suspensions on the vehicle dynamic behaviour. To do this, 144 dynamic simulations were performed modifying, one at a time, the stiffness and damping coefficients, of the primary and secondary suspensions. Three values were assigned to each parameter, corresponding to the percentiles 10, 50 and 90 of a data set stored in a database of railway vehicles.After processing the results of these simulations, the analyzed parameters were sorted by increasing influence. It was also found which of these parameters could be estimated with a lesser degree of accuracy in future simulations without appreciably affecting the simulation results. In general terms, it was concluded that the highest influences were found for the longitudinal stiffness and the lateral stiffness of the primary suspension, and the lowest influences for the vertical stiffness and the vertical damping of the primary suspension, with the parameters of the secondary suspension showing intermediate influences between them.

Recursos intangibles como factores clave en la gestión estratégica de instituciones de educación superior y su impacto en los procesos de innovación

La presente investigación, tiene como objetivo analizar las influencias que ejercen los recursos intangibles (Gestión del Conocimiento, Marca, Reputación Organizacional y Responsabilidad Social) en la gestión estratégica de las instituciones de educación superior (IES) y el impacto de los mismos en los procesos de innovación a través del valor añadido que se transfiere al entorno. Se considera importante realizar un estudio sobre este tema dado que son las IES las encargadas de proporcionar los conocimientos y los nuevos hallazgos en innovaciones tecnológicas, que son transferidas al tejido productivo de las regiones, lo que proporciona crecimiento económico y mejoras en la calidad de vida. El estudio se enmarca dentro de los postulados de la teoría de los recursos y las capacidades (TRC) y de los intangibles, los cuales sirven de base a la investigación. Se planteó un sistema de hipótesis subdividido en dos vías de influencias. La primera, donde se analizan las influencias directas que ejercen los recursos intangibles sobre los resultados de las IES. La otra vía es la indirecta, que estudia las influencias que ejercen los recursos intangibles gestionados estratégicamente sobre los resultados de las IES. Esta investigación se ha concebido como no experimental, de tipo exploratorio, basada en el paradigma que busca explicar un fenómeno (variable dependiente) a través del comportamiento de las variables independientes. Es un estudio transversal, cuantitativo, que intenta describir las causas del fenómeno. Con el objeto de determinar las influencias o relaciones de causalidad que subyacen entre las variables, se utilizó la técnica del modelo de ecuaciones estructurales (SEM). La población objeto de estudio estuvo constituida por los 857 individuos pertenecientes a los consejos directivos de las IES, que forman parte de las base de datos que gestiona el Consorcio de Escuelas de Ingeniería de Latinoamérica y del Caribe y la Universidad Politécnica de Madrid, con un tamaño de muestra significativa de 250 directivos, lo que representa el 29,42% de la población. Como fuentes de recolección de información se utilizaron fuentes primarias y secundarias. Para recabar la información primaria se diseñó un cuestionario (ad hoc), el cual fue validado por expertos. La información de fuentes secundarias se extrajo de la bases de datos de la Red Iberoamericana de Ciencia y Tecnología (RICYT). Los resultados obtenidos indican que las influencias directas que pueden ejercer los recursos intangibles (Gestión del Conocimiento, Marca, Reputación Organizacional y Responsabilidad Social) no son significativas, por ello se rechazaron todas las hipótesis de la vía de influencia directa. Asimismo, de acuerdo con el contraste realizado al submodelo que representa la vía de influencia indirecta, resultaron significativas las influencias que ejercen los intangibles Gestión del Conocimiento y Reputación Organizacional, gestionadas estratégicamente sobre los resultados con valor añadido generado por las IES y transferidos al entorno. Sin embargo, no se apoyan todas las hipótesis del modelo, debido a que los constructos Marca y Responsabilidad Social resultaron no significativos. Las teorías sobre intangibles enmarcadas en la TRC no son del todo robustas y requieren de mayores esfuerzos por parte de los investigadores para lograr definir los constructos a utilizar. De igual forma, se sigue corroborando el desfase que existe entre las teorías que sustentan la investigación y las comprobaciones empíricas de las mismas. Además, se evidencia que las IES enfocan su actuación hacia la academia, por encima de las otras funciones, otorgando a la enseñanza e investigación y a la reputación organizacional una mayor importancia. Sin embargo, debido a su naturaleza no empresarial, las IES siguen manteniendo una filosofía de gestión enfocada a la generación y transmisión de conocimientos que crean reputación. Se excluyen los intangibles Marca y Responsabilidad Social, por considerar que no aportan valor a sus procesos internos o que están inmersos dentro de otros recursos intangibles. En conclusión, se corrobora el atraso de la gestión estratégica que presentan las IES en Latinoamérica. Se comprueba la no aplicación de postulados básicos de la gerencia moderna que contribuyan al manejo eficiente de todos sus recursos y al logro de sus objetivos. Esto deriva en la necesidad de modernizar la visión estratégica de las IES y en crear mejores mecanismos para lograr reconocer, mantener, proteger y desarrollar los Recursos Intangibles que poseen, realizando combinaciones de recursos óptimas, que maximicen la creación de valor para sí mismas y para la sociedad a la que pertenecen. ABSTRACT This research aims to analyze the influences exerted by intangible resources (Knowledge Management, Brand, Organizational Reputation and Social Responsibility) in the strategic management of higher education institutions (HEIs) and their impact in the innovation processes through the added value that is transferred to the environment. It is considered important to conduct a study on this issue since HEIs are responsible for providing knowledge and new findings on technological innovations, which are then, transferred to the productive fabric of these regions, providing economic growth and improvements in quality of life. The study is framed within the tenets of the Theory of Resources and Capabilities (TRC) and of intangibles which underlie this research. A system of hypotheses was raised which was subdivided into two pathways of influences. In the first system the direct influences exerted by intangible resources on the results of the IES are analyzed. The other system focuses on the indirect influences exerted by the strategically managed intangible resources on the HEIs results. This research is designed as experimental, exploratory and based on the paradigm that seeks to explain a phenomenon (the dependent variable) through the behavior of the independent variables. It is a crosssectional, quantitative study, which attempts to describe the causes of the phenomenon. In order to determine the influences or causal relationships among variables the structural equation modeling technique (SEM) was used. The population under study consisted of 857 individuals from the boards of HEIs, which are part of the database managed by the Consortium of Engineering Schools in Latin America and the Caribbean and the Technical University of Madrid, with a significant sample size of 250 managers which represents 29.42% of the population. As sources of information gathering primary and secondary sources were used. To collect primary information an ad-hoc questionnaire which was validated by experts was designed. The secondary information was extracted from the database of the Latin American Network of Science and Technology (RICYT). The results obtained indicate that the direct influences that intangible resources (Knowledge Management, Brand, Organizational Reputation and Social Responsibility) can exert are not significant. Therefore, all hypotheses related to direct influence were rejected. Also, according to the test made with the system which represents the indirect channel of influence, significant influences were exerted on the results with added value generated by the HEIs by the intangibles Knowledge Management and Organizational Reputation when they were managed strategically. However, all model hypotheses are not supported, because the constructs Brand and Social Responsibility were not significant. Theories of intangibles within the framework of the Theory of Resources and Capabilities are not entirely robust and require greater efforts by researchers to define the constructs to be used. Similarly the existing gap between the theories underpinning research and the empirical tests continues to be corroborated. In addition, there is evidence that HEIs focus their action on the academy neglecting the other functions, giving more importance to teaching, research and organizational reputation. However, due to their non-business nature, HEIs still maintain a management philosophy focused on the generation and transmission of knowledge which leads to reputation. The intangibles Brand and Social Responsibility are excluded, considering that they do not add value to their internal processes or are embedded within other intangible resources. In conclusion, the backwardness of HEIs’ strategic management in Latin America is confirmed. The lack of application of the basic principles of modern management that contribute to the efficient administration of all the resources and the achievement of objectives is proven. This leads to the need to modernize the strategic vision of HEIs and the need for better mechanisms to recognize, maintain, protect and develop the intangible resources they possess, achieving optimal combinations of resources in order to maximize the creation of value for them and for the society to which they belong.

Experimental hemochromatosis due to MHC class I HFE deficiency: Immune status and iron metabolism

The puzzling linkage between genetic hemochromatosis and histocompatibility loci became even more so when the gene involved, HFE, was identified. Indeed, within the well defined, mainly peptide-binding, MHC class I family of molecules, HFE seems to perform an unusual yet essential function. As yet, our understanding of HFE function in iron homeostasis is only partial; an even more open question is its possible role in the immune system. To advance on both of these avenues, we report the deletion of HFE α1 and α2 putative ligand binding domains in vivo. HFE-deficient animals were analyzed for a comprehensive set of metabolic and immune parameters. Faithfully mimicking human hemochromatosis, mice homozygous for this deletion develop iron overload, characterized by a higher plasma iron content and a raised transferrin saturation as well as an elevated hepatic iron load. The primary defect could, indeed, be traced to an augmented duodenal iron absorption. In parallel, measurement of the gut mucosal iron content as well as iron regulatory proteins allows a more informed evaluation of various hypotheses regarding the precise role of HFE in iron homeostasis. Finally, an extensive phenotyping of primary and secondary lymphoid organs including the gut provides no compelling evidence for an obvious immune-linked function for HFE.

A link between protein structure and enzyme catalyzed hydrogen tunneling

We present evidence that the size of an active site side chain may modulate the degree of hydrogen tunneling in an enzyme-catalyzed reaction. Primary and secondary kH/kT and kD/kT kinetic isotope effects have been measured for the oxidation of benzyl alcohol catalyzed by horse liver alcohol dehydrogenase at 25°C. As reported in earlier studies, the relationship between secondary kH/kT and kD/kT isotope effects provides a sensitive probe for deviations from classical behavior. In the present work, catalytic efficiency and the extent of hydrogen tunneling have been correlated for the alcohol dehydrogenase-catalyzed hydride transfer among a group of site-directed mutants at position 203. Val-203 interacts with the opposite face of the cofactor NAD+ from the alcohol substrate. The reduction in size of this residue is correlated with diminished tunneling and a two orders of magnitude decrease in catalytic efficiency. Comparison of the x-ray crystal structures of a ternary complex of a high-tunneling (Phe-93 → Trp) and a low-tunneling (Val-203 → Ala) mutant provides a structural basis for the observed effects, demonstrating an increase in the hydrogen transfer distance for the low-tunneling mutant. The Val-203 → Ala ternary complex crystal structure also shows a hyperclosed interdomain geometry relative to the wild-type and the Phe-93 → Trp mutant ternary complex structures. This demonstrates a flexibility in interdomain movement that could potentially narrow the distance between the donor and acceptor carbons in the native enzyme and may enhance the role of tunneling in the hydride transfer reaction.

Characteristics of virus-specific CD8+ T cells in the liver during the control and resolution phases of influenza pneumonia

Dissection of the primary and secondary response to an influenza A virus established that the liver contains a substantial population of CD8+ T cells specific for the immunodominant epitope formed by H-2Db and the influenza virus nucleoprotein peptide fragment NP366–374 (DbNP366). The numbers of CD8+ DbNP366+ cells in the liver reflected the magnitude of the inflammatory process in the pneumonic lung, though replication of this influenza virus is limited to the respiratory tract. Analysis of surface phenotypes indicated that the liver CD8+ DbNP366+ cells tended to be more “activated” than the set recovered from lymphoid tissue but generally less so than those from the lung. The distinguishing characteristic of the lymphocytes from the liver was that the prevalence of the CD8+ DbNP366+ set was always much higher than the percentage of CD8+ T cells that could be induced to synthesize interferon γ after short-term, in vitro stimulation with the NP366–374 peptide, whereas these values were generally comparable for virus-specific CD8+ T cells recovered from other tissue sites. Also, the numbers of apoptotic CD8+ T cells were higher in the liver. The results overall are consistent with the idea that antigen-specific CD8+ T cells are destroyed in the liver during the control and resolution phases of this viral infection, though this destruction is not necessarily an immediate process.

Radiation-induced Release of Transforming Growth Factor α Activates the Epidermal Growth Factor Receptor and Mitogen-activated Protein Kinase Pathway in Carcinoma Cells, Leading to Increased Proliferation and Protection from Radiation-induced Cell Death

Exposure of A431 squamous and MDA-MB-231 mammary carcinoma cells to ionizing radiation has been associated with short transient increases in epidermal growth factor receptor (EGFR) tyrosine phosphorylation and activation of the mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) pathways. Irradiation (2 Gy) of A431 and MDA-MB-231 cells caused immediate primary activations (0–10 min) of the EGFR and the MAPK and JNK pathways, which were surprisingly followed by later prolonged secondary activations (90–240 min). Primary and secondary activation of the EGFR was abolished by molecular inhibition of EGFR function. The primary and secondary activation of the MAPK pathway was abolished by molecular inhibition of either EGFR or Ras function. In contrast, molecular inhibition of EGFR function abolished the secondary but not the primary activation of the JNK pathway. Inhibition of tumor necrosis factor α receptor function by use of neutralizing monoclonal antibodies blunted primary activation of the JNK pathway. Addition of a neutralizing monoclonal antibody versus transforming growth factor α (TGFα) had no effect on the primary activation of either the EGFR or the MAPK and JNK pathways after irradiation but abolished the secondary activation of EGFR, MAPK, and JNK. Irradiation of cells increased pro-TGFα cleavage 120–180 min after exposure. In agreement with radiation-induced release of a soluble factor, activation of the EGFR and the MAPK and JNK pathways could be induced in nonirradiated cells by the transfer of media from irradiated cells 120 min after irradiation. The ability of the transferred media to cause MAPK and JNK activation was blocked when media were incubated with a neutralizing antibody to TGFα. Thus radiation causes primary and secondary activation of the EGFR and the MAPK and JNK pathways in autocrine-regulated carcinoma cells. Secondary activation of the EGFR and the MAPK and JNK pathways is dependent on radiation-induced cleavage and autocrine action of TGFα. Neutralization of TGFα function by an anti-TGFα antibody or inhibition of MAPK function by MEK1/2 inhibitors (PD98059 and U0126) radiosensitized A431 and MDA-MB-231 cells after irradiation in apoptosis, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and clonogenic assays. These data demonstrate that disruption of the TGFα–EGFR–MAPK signaling module represents a strategy to decrease carcinoma cell growth and survival after irradiation.

Characterization of serum amyloid A protein mRNA expression and secondary amyloidosis in the domestic duck

Secondary amyloidosis is a common disease of water fowl and is characterized by the deposition of extracellular fibrils of amyloid A (AA) protein in the liver and certain other organs. Neither the normal role of serum amyloid A (SAA), a major acute phase response protein, nor the causes of secondary amyloidosis are well understood. To investigate a possible genetic contribution to disease susceptibility, we cloned and sequenced SAA cDNA derived from livers of domestic ducks. This revealed that the three C-terminal amino acids of SAA are removed during conversion to insoluble AA fibrils. Analysis of SAA cDNA sequences from several animals identified a distinct genetic dimorphism that may be relevant to susceptibility to secondary amyloid disease. The duck genome contained a single copy of the SAA gene that was expressed in liver and lung tissue of ducklings, even in the absence of induction of acute phase response. Genetic analysis of heterozygotes indicated that only one SAA allele is expressed in livers of adult birds. Immunofluorescence staining of livers from adult ducks displaying early symptoms of amyloidosis revealed what appear to be amyloid deposits within hepatocytes that are expressing unusually high amounts of SAA protein. This observation suggests that intracellular deposition of AA may represent an early event during development of secondary amyloidosis in older birds.