Search

[EN] Novel diastereomeric triads containing two naphthalene chromophores have been designed in which an electron-donating amine moiety is covalently integrated into the connecting bridge. Photophysical studies (steady-state and time-resolved fluorescence) in solvents of different polarity have been performed. A remarkable stereodifferentiation in the intramolecular fluorescence quenching was found in acetonitrile. Laser flash photolysis gave rise to naphthalene-derived radical cations, which were also quenched by the amine with an even higher degree of stereodifferentiation. The results are in agreement with thermodynamic estimations and indicate that photoinduced electron transfer (PET) is the main quenching pathway. Furthermore, theoretical calculations have allowed us to explain the experimentally observed stereodifferentiation in PET quenching.

In the present work, the nematic glassy state of the non-symmetric LC dimer -(4-cyanobiphenyl-4-yloxy)--(1-pyrenimine-benzylidene-4-oxy) undecane is studied by means of calorimetric and dielectric measurements. The most striking result of the work is the presence of two different glass transition temperatures: one due to the freezing of the flip-flop motions of the bulkier unit of the dimer and the other, at a lower temperature, related to the freezing of the flip-flop and precessional motions of the cyanobiphenyl unit. This result shows the fact that glass transition is the consequence of the freezing of one or more coupled dynamic disorders and not of the disordered phase itself. In order to avoid crystallization when the bulk sample is cooled down, the LC dimer has been confined via the dispersion of -alumina nanoparticles, in several concentrations.

In the present work, the nematic glassy state of the non-symmetric LC dimer -(4-cyanobiphenyl-4-yloxy)--(1-pyrenimine-benzylidene-4-oxy) undecane is studied by means of calorimetric and dielectric measurements. The most striking result of the work is the presence of two different glass transition temperatures: one due to the freezing of the flip-flop motions of the bulkier unit of the dimer and the other, at a lower temperature, related to the freezing of the flip-flop and precessional motions of the cyanobiphenyl unit. This result shows the fact that glass transition is the consequence of the freezing of one or more coupled dynamic disorders and not of the disordered phase itself. In order to avoid crystallization when the bulk sample is cooled down, the LC dimer has been confined via the dispersion of -alumina nanoparticles, in several concentrations., Postprint (published version)

How the positional values along the proximo-distal axis (stylopod-zeugopod-autopod) of the limb are specified is intensely debated. Early work suggested that cells intrinsically change their proximo-distal positional values by measuring time. Recently, however, it is suggested that instructive extrinsic signals from the trunk and apical ectodermal ridge specify the stylopod and zeugopod/autopod, respectively. Here, we show that the zeugopod and autopod are specified by an intrinsic timing mechanism. By grafting green fluorescent protein-expressing cells from early to late chick wing buds, we demonstrate that distal mesenchyme cells intrinsically time Hoxa13 expression, cell cycle parameters and the duration of the overlying apical ectodermal ridge. In addition, we reveal that cell affinities intrinsically change in the distal mesenchyme, which we suggest results in a gradient of positional values along the proximo-distal axis. We propose a complete model in which a switch from extrinsic signalling to intrinsic timing patterns the vertebrate limb.

Con el paso del tiempo Internet se ha introducido en la sociedad convirtiéndose en un elemento fundamental para estar actualizados en cualquier ámbito y, como no podía ser menos en el sector empresarial, ha entrado con gran fuerza. Las empresas han dado el salto al mundo online creando sitios webs en los que vender sus productos u ofrecer sus servicios e incluso llegando a aparecer negocios con carácter puramente online. Al hilo de todo esto surge la necesidad de realizar un análisis completo de todas las acciones que se realizan dentro de un sitio web, conociendo así el comportamiento de los usuarios que lo visitan y otros datos con los que poder mejorar las estrategias online que proponen las empresas y obtener mayores beneficios. De esta forma es como surge el concepto que analizamos en este trabajo, la Analítica Web. En el desarrollo de este Trabajo Fin de Grado conoceremos las estrategias que realizan las empresas para posicionarse mejor en la web y las herramientas que se pueden usar para ello, además analizaremos la importancia de las redes sociales para las empresas. Se pretende exponer detalladamente en qué consiste la Analítica Web, cómo surgió y cuáles son las mejores herramientas existentes.

The photooxygenation of model compounds containing the two enantiomers of naproxen (NPX) covalently linked to histidine (His), tryptophan (Trp) and tyrosine (Tyr) has been investigated by steady state irradiation, fluorescence spectroscopy and laser flash photolysis. The NPX–His systems presented the highest oxygen-mediated photoreactivity. Their fluorescence spectra matched that of isolated NPX and showed a clear quenching by oxygen, leading to a diminished production of the NPX triplet excited state ( 3 NPX*–His). Analysis of the NPX–His and NPX–Trp photolysates by UPLC-MS–MS revealed in both cases the formation of two photoproducts, arising from the reaction of singlet oxygen (1 O2) with the amino acid moiety. The most remarkable feature of NPX–Trp systems was a fast and stereoselective intramolecular fluorescence quenching, which prevented the efficient formation of 3 NPX*–Trp, thus explaining their lower reactivity towards photooxygenation. Finally, the NPX–Tyr systems were nearly unreactive and exhibited photophysical properties essentially coincident with those of the parent NPX. Overall, these results point to a type II photooxygenation mechanism, triggered by generation of 1 O2 from the 3 NPX* chromophore

[EN] Cholesterol (Ch) is one of the most important building blocks of cell membranes. It is also one of the main targets for oxidation via Type I hydrogen abstraction (HA), which leads to a variety of physiological consequences in the human body. To provide a deeper understanding of the oxidation mechanism, steady-state 1H CIDNP, steady-state and laser-flash photolysis in combination with quantum mechanical calculations were applied to study HA in three model systems. The experiments involved photoinduced reactions in a cholesterol–benzophenone mixture and two derivatives, in which aminocholestene and benzophenone are covalently coupled yielding a dyad. It has been found, that a specific orientation of the benzophenone moiety toward the allylic hydrogens of cholesterol/aminocholestene is crucial for the efficient HA. Such a confined topology may play an important role for the particular oxidation of Ch in cell membranes., [ES] El colesterol (Ch) es uno de los componentes más importantes de la membrana celular. Además es una diana para la oxidación Tipo I mediante abstracción de hidrógeno (AH), conduciendo a consecuencias fisiológicas adversas. Para profundizar en la comprensión del mecanismo de oxidación, se han realizado estudios de fotólisis en estado estacionario y de destello láser ,H-CIDNP en combinación con cálculos de mecánica cuántica con el fin de estudiar la AH en tres sistemas modelo. Los experimentos implican reacciones fotoinducidas en una mezcla de colesterol-benzofenona y dos derivados, en los que el aminocolesteno y la benzofenona están acoplados covalentemente produciendo una diada. Así, se ha demostrado, que la orientación específica de la fracción de benzofenona hacia los hidrógenos alílicos de colesterol / aminocolesteno es crucial para una eficiente AH. Estos factores topológicos pueden desempeñar un papel importante en la oxidación del Ch en las membranas celulares. (español)

Metamizole is a pain-killer drug that has been banned in some countries because of its toxicity, but it is still used in many countries due to its effective analgesic and antispasmodic properties. Although large variability in the biodisposition and adverse effects of metamizole are known, factors underlying this variability are poorly understood. We analyzed the urinary recovery of metabolites, as well as the association of these profiles with genetic and non-genetic factors, in a group of 362 healthy individuals. Gender and functional polymorphisms are strongly related to metabolic profiles. N-demethylation of the active metabolite MAA is diminished in carriers of the CYP2C19*2 allele and in NAT2-slow acetylators. Acetylation of the secondary metabolite AA is decreased in men, in drinkers and in NAT2-slow acetylators with a differential effect of NAT2*5 and NAT2*6 alleles. The formylation of MAA is diminished in older subjects and in carriers of defect CYP2C9 and CYP2C19 alleles. Two novel arachidonoyl metabolites were identified for the first time in humans. Women and NAT2-slow acetylators show higher concentrations, whereas the presence of the rapid CYP2C19*17 allele is associated with lower concentrations of these metabolites. All genetic associations show a gene-dose effect. We identified for the first time genetic and non-genetic factors related to the oxidative metabolism of analgesic drug metamizole, as well as new active metabolites in humans. The phenotypic and genetic factors identified in this study have a potential application as biomarkers of metamizole biotransformation and toxicity.

[EN] The goal of this study is to determine the economic value (implicit price) that consumers give to different characteristics with influence in the purchase decision of traditional varieties of tomatoes. To accomplish this aim three hedonic price models have been estimated with data obtained from an experi-mental auction where participants should bid and value hedonically the tomatoes. The results point to a re-lationship between the price and the income level of the participants, as well as the tomato hedonic ratings., [ES] El presente trabajo tiene como objetivo determinar el valor económico (precio implícito) que otorgan los consumidores a diversas características influyentes en la decisión de compra de tomates de variedades tradicionales. Para ello se han estimado tres modelos de precios hedónicos con datos obtenidos a partir de una subasta experimental en la que los participantes, además de pujar por los tomates del estudio, debían realizar una valoración hedónica de los mismos. Los resultados apuntan hacia una relación entre el precio y el nivel de renta de los participantes, así como con la valoración hedónica que hacen de los tomates.

The formation and maintenance of the apical ectodermal ridge (AER) is critical for the outgrowth and patterning of the vertebrate limb. The induction of the AER is a complex process that relies on integrated interactions among the Fgf, Wnt, and Bmp signaling pathways that operate within the ectoderm and between the ectoderm and the mesoderm of the early limb bud. The transcription factors Sp6 and Sp8 are expressed in the limb ectoderm and AER during limb development. Sp6 mutant mice display a mild syndactyly phenotype while Sp8 mutants exhibit severe limb truncations. Both mutants show defects in AER maturation and in dorsal-ventral patterning. To gain further insights into the role Sp6 and Sp8 play in limb development, we have produced mice lacking both Sp6 and Sp8 activity in the limb ectoderm. Remarkably, the elimination or significant reduction in Sp6;Sp8 gene dosage leads to tetra-amelia; initial budding occurs, but neither Fgf8 nor En1 are activated. Mutants bearing a single functional allele of Sp8 (Sp6−/−;Sp8+/−) exhibit a split-hand/foot malformation phenotype with double dorsal digit tips probably due to an irregular and immature AER that is not maintained in the center of the bud and on the abnormal expansion of Wnt7a expression to the ventral ectoderm. Our data are compatible with Sp6 and Sp8 working together and in a dose-dependent manner as indispensable mediators of Wnt/ßcatenin and Bmp signaling in the limb ectoderm. We suggest that the function of these factors links proximal-distal and dorsal-ventral patterning.

The photophysical and photochemical behavior of (R)-cinacalcet (CIN) and (S)-naproxen (NPX) entrapped within liposomes has been studied. For this purpose, liposome encapsulated drugs have been prepared through thin layer evaporation and characterized by transmission electron microscopy, cryoscopy scanning electron microscopy and dynamic light scattering. Steady state and time-resolved fluorescence experiments showed similar spectra, emission quantum yields, singlet energies and lifetimes for the selected drugs, outside and inside liposomes. By contrast, laser flash photolysis experiments revealed an important enhancement of the triplet lifetimes for entrapped drugs inside liposomes, indicating the spatial confinement existing in the microenvironment prevailing in these biomimetic entities. Thus, this photophysical property shows potential as a non-invasive, direct and valuable tool to monitor encapsulation of photoactive drugs and to probe the intraliposome environment. In addition, it provides a new quantitative indicator of the capability of liposomes to act as drug carriers.

[Background]: Precise temporal and spatial expression of the clustered Hox genes is essential for patterning the developing embryo. Temporal activation of Hox genes was shown to be cluster-autonomous. However, gene clustering appears dispensable for spatial colinear expression. Generally, a set of Hox genes expressed in a group of cells instructs these cells about their fate such that the differential expression of Hox genes results in morphological diversity. The spatial colinearity is considered to rely both on local and long-range cis regulation. [Results]: Here, we report on the global deregulation of HoxA and HoxD expression patterns upon inactivation of a subset of HOXA and HOXD proteins. [Conclusions]: Our data suggest the existence of a >self-regulation> mechanism, a process by which HOX proteins establish and/or maintain the spatial domains of the Hox gene family and we propose that the functionally dominant HOX proteins could contribute to generating the spatial parameters of Hox expression in a given tissue, i.e., HOX controlling the establishment of the ultimate HOX code.

The HoxdDel(11-13) mutant is one of the animal models for human synpolydactyly, characterized by short and syndactylous digits. Here we have characterized in detail the cartilage and bone defects in these mutants. We report two distinct phenotypes: (i) a delay and change in pattern of chondrocyte maturation of metacarpals/metatarsals and (ii) formation of a poor and not centrally positioned primary ossification center in the proximal-intermediate phalanx. In the metacarpals of HoxdDel(11-13) mutants, ossification occurs postnataly, in the absence of significant Ihh expression and without the establishment of growth plates, following patterns similar to those of short bones. The strong downregulation in Ihh expression is associated with a corresponding increase of the repressor form of Gli3. To evaluate the contribution of this alteration to the phenotype, we generated double HoxdDel(11-13);Gli3 homozygous mutants. Intriguingly, these double mutants showed a complete rescue of the phenotype in metatarsals but only partial phenotypic rescue in metacarpals. Our results support Hox genes being required in a dose-dependent manner for long bone cartilage maturation and suggest that and excess of Gli3R mediates a significant part of the HoxdDel(11-13) chondrogenic phenotype.

A new direct and noninvasive methodology based on transient absorption spectroscopy has been developed to probe the feasibility of drug-drug interactions within a common protein binding site. The simultaneous presence of (R)-cinacalcet (CIN) and (S)-propranolol (PPN) within human or bovine alpha(1)-acid glycoproteins (AAGs) is revealed by detection of (CIN)-C-3* as the only transient species after laser flash photolysis of CIN/PPN/AAG mixtures at 308 nm. This is the result of triplet-triplet energy transfer from (PPN)-P-3* to CIN, which requires close contact between the two drugs within the same biological compartment. Similar results are obtained with nabumetone and CIN as donor/acceptor partners. This new methodology can, in principle, be extended to a variety of drug/drug/biomolecule combinations.

It is shown how chemically induced dynamic nuclear polarisation (CIDNP) spectroscopy is able to efficiently complement electron paramagnetic resonance (EPR), when molecular transformations of free radical pairs are investigated. This is demonstrated in three examples of modelling biologically relevant phenomena, particularly oxidative stress and antioxidant activity. Lipid peroxidation, topological control in the oxidation of cholesterol, and a mechanistic study of antioxidant activity of natural tea and wine polyphenols are presented.

New photoactive dyads have been synthesized by derivatization of cholic acid (CA) or cholesterol (Ch). These compounds have proven to be efficient tools to monitor incorporation of CA and Ch to mixed micelles (MM) and to probe the microenvironment experienced inside these entities. The outstanding capability of MM to solubilize Ch has been demonstrated.

Cholesterol is one of the most important building blocks of cell membranes. It is also one of the main targets for oxidation via Type I hydrogen abstraction (HA), which leads to a variety of physiological consequences in the human body. To provide a deeper understanding of the oxidation mechanism, steady-state H-1 CIDNP, steady-state and laser-flash photolysis in combination with quantum mechanical calculations were applied to study HA in three model systems. The experiments involved photoinduced reactions in a cholesterol-benzophenone mixture and two derivatives, in which aminocholestene and benzophenone are covalently coupled yielding a dyad. It has been found, that a specific orientation of the benzophenone moiety toward the allylic hydrogens of cholesterol/aminocholestene is crucial for the efficient HA. Such a confined topology may play an important role for the particular oxidation of cholesterol in cell membranes.

Este plan de calidad se ha desarrollado con el fin de presentar nuestra empresa a licitaciones de obras/proyectos; en consecuencia es un documento de orden externo en el que se indica la forma en la que CASANOVA EQUIPAMIENTO TURÍSTICO Y URBANO, S.A. cumple todos los requisitos de la norma y las especificaciones del cliente en las instalaciones que realiza. El objeto del presente Plan de Calidad y Ambiental es establecer, documentar, implementar y mantener al día un sistema de gestión de la calidad y ambiental como medio que asegure la conformidad de los productos y servicios, realizados por CASANOVA EQUIPAMIENTOS TURÍSTICOS Y URBANOS S.A., dentro de un contexto de mejora continua del sistema de gestión de la calidad y ambiental con el objeto de: -Obtener productos y servicios con unas características finales capaces de incrementar la satisfacción de los clientes y minimizar los daños o impactos causados al medio ambiente por sus actividades pasadas, presentes y futuras, las cuales deben ser acordes con la política de la calidad y ambiental de la empresa y con los objetivos y metas derivados de ella. -Demostrar su capacidad para realizar productos y servicios conformes, competitivos y acordes con los requisitos reglamentarios que les fueran aplicables.

¿Cómo entender la discriminación en el ámbito empresarial?, ¿cómo pensar las prácticas discriminatorias de sujetos concretos en el marco de empresas que institucionalmente no lo son? Es decir, ¿cómo interpretar la discriminación que se produce informalmente en las acciones o decisiones cotidianas de las personas? Analiza las formas de discriminación, por género, raza, edad, nivel socioeconómico e identidad sexual, en el entorno laboral de las pequeñas, medianas y grandes empresas ubicadas en Lima Metropolitana. La necesidad de comprender más a fondo lo que ocurre dentro de las empresas en nuestro país, los esfuerzos que vienen realizando estas para promover la diversidad dentro de sus organizaciones y los aspectos que aún falta conocer y analizar respecto al tema, fueron los grandes impulsores del proyecto cuyos resultados nos brindan una primera aproximación acerca de lo que las empresas y sus trabajadores opinan, observan y hacen al respecto.

Photophysical techniques, specifically time-resolved fluorescence and laser flash photolysis, have proven to be noninvasive, straightforward, and valuable tools to demonstrate how drug encapsulation into biomimetic mixed micelles (MM) influences the dynamics of excited states and their accessibility to ionic quenchers. This concept has been illustrated by choosing a set of currently administered drugs containing a common naphthalene chromophore, namely, (S)-naproxen and its methyl ester, (R)-cinacalcet and (S)-propranolol. A remarkable increase of their triplet lifetimes is noticed when experiments are performed in MM, indicating efficient entrapment of the drugs in these supramolecular entities. Furthermore, a decrease of 1 order of magnitude in the quenching rate constant of the singlet and triplet excited states (by iodide or nitrite, respectively) is observed upon encapsulation into MM. This approach can in principle be extended to other microenvironments capable of incorporating photoactive compounds. © 2013 American Chemical Society.

La formación por competencias se basa en la necesidad de una mayor adaptación y desarrollo de los futuros profesionales a las demandas y cambios sociales. Se centra en el aprendizaje y no en la enseñanza, en alcanzar resultados de aprendizaje integrando el saber, saber hacer, saber estar y saber ser. La simulación clínica surge como un nuevo método de aprendizaje y de evaluación para aprender y valorar conocimientos, habilidades (técnicas y no técnicas) y actitudes en el ámbito de las ciencias de la salud. La simulación recrea un escenario, lo más fiel a la realidad y permite que los alumnos puedan resolver un caso clínico y, los profesores puedan analizar y evaluar la actuación. El entrenamiento con la simulación favorece la seguridad de los pacientes y evita el error. Esta metodología innovadora, posibilita la consecución de las competencias profesionales, el desarrollo de las capacidades intelectuales y psicomotoras de los estudiantes, con mayor preparación, más confianza y más seguridad... Competency training is based on the need for further adaptation and development of future professionals to meet demands and social changes. It focuses on learning rather than teaching, in achieving learning (education) goals by integrating knowledge, knowhow, good behavior and being oneself. Clinical simulation emerges as a new method of learning and assessment of knowledge, skills (technical and non-technical) and attitudes in the field of health sciences. The simulation recreates a scenario, closer to reality, and enables students to solve clinical cases and allows teachers to be able to analyze and evaluate their performance. The simulation training promotes patient safety and helps in avoiding errors. This innovative methodology enables the assessment of professional competency, the development of intellectual and psychomotor skills for students, in order to be more prepared, more confident and more reliable...