Synthesis of cyclometalated gold (III) complexesfunctionalized by alkynyl derivatives. Study of the interaction with DNA secondary structures.

This thesis explores the synthesis of cyclometalated gold(III) complexes functionalized by alkynyl ligands, as well as the study of the interaction of the studied complexes with DNA secondary structures. In this work, bidentate and tridentate ligands, in particular derived from both phenylpyridine and diphenylpyridine, respectively, have been employed as framework structure in order to stabilize the studied gold complexes. Chapter 1 studies the synthesis of cyclometalated gold(III) complexes functionalized by alkynyl derivatives. The main feature of the employed alkynyl derivatives was its functionalization by amino ester terminal groups, suitable to be converted to amino acids, which are overexpressed in cells and may promote the interaction of the studied complexes with DNA. Chapter 2 explores a study of the interaction of the synthesized gold(III) complexes with DNA secondary structures. Making use of a variety of analytical techniques, such as circular dichroism (CD), FRET melting experiments, FRET titration and UV difference spectrum, we have observed that a selection of the studied gold complexes may exert interaction with certain DNA secondary structure in physiological media. Chapter 3 reports the attempts to conduct the synthesis of a family of cyclometallated (C^N) gold(III) complexes capable of bearing two functionalisable substituents. In recent years, our research group has proven the excellent reactivity of certain tridentate (C^N^C) gold (III) complexes as mild base, allowing C–H or N–H activation to synthesize gold aryls, alkynyls and heteoaryls derivatives. However, the rigidity of the tridentate framework has limitated the reactivity of this system. Accordingly, the aim of this chapter is the synthesis of bidentate gold (III) derivatives, which may provide a wide range of reactivity possibilities because of the presence of two functionalisable positions

Las cooperativas en las cadenas de valor del café en Guatemala: su contribución al logro de objetivos sociales, laborales y ambientales

The world economy is currently made up of “integrated supply chains, where more than half of total imports of manufactured goods, and more than 70 percent of total service imports are intermediate goods or  services” (Lagarde, 2014). This study proposes a value chain model based on both the business perspective -traditional versus sustainable- and the governance mechanisms -centralized versus decentralized- that characterize them. The aim is to explore the role that cooperatives adopt in the coffee value chains in Guatemala and how chains led by cooperatives may differ from those led by investors. The work suggests that cooperatives contribute to building sustainable and relational value chains with a triple bottom line that includes social, labour and environmental objectives.La economía mundial está actualmente constituida por “cadenas de suministro integradas, donde más de la mitad de las importaciones totales de bienes manufacturados, y más del 70 por ciento de las importaciones totales de servicios, son bienes o servicios intermedios” (Lagarde, 2014). Este estudio propone un modelo de cadenas de valor en base a la perspectiva empresarial -tradicional versus sostenible- y los mecanismos de gobernanza -centralizados versus descentralizados- que las caracterizan. El objetivo es explorar el papel que adoptan las cooperativas en las cadenas de valor de café en Guatemala y de qué manera las cadenas de valor lideradas por cooperativas pueden diferir de aquellas dirigidas por inversores. El trabajo plantea que las cooperativas aportan a la construcción de cadenas de valor sostenibles y relacionales, con una triple línea de base que incluye objetivos sociales, laborales y ambientales

Persistence and generalization of adaptive changes in auditory localization behavior following unilateral conductive hearing loss

Introduction: Sound localization relies on the neural processing of binaural and monaural spatial cues generated by the physical properties of the head and body. Hearing loss in one ear compromises binaural computations, impairing the ability to localize sounds in the horizontal plane. With appropriate training, adult individuals can adapt to this binaural imbalance and largely recover their localization accuracy. However, it remains unclear how long this learning is retained or whether it generalizes to other stimuli. Methods: We trained ferrets to localize broadband noise bursts in quiet conditions and measured their initial head orienting responses and approach-to-target behavior. To evaluate the persistence of auditory spatial learning, we tested the sound localization performance of the animals over repeated periods of monaural earplugging that were interleaved with short or long periods of normal binaural hearing. To explore learning generalization to other stimulus types, we measured the localization accuracy before and after adaptation using different bandwidth stimuli presented against constant or amplitude-modulated background noise. Results: Retention of learning resulted in a smaller initial deficit when the same ear was occluded on subsequent occasions. Each time, the animals’ performance recovered with training to near pre-plug levels of localization accuracy. By contrast, switching the earplug to the contralateral ear resulted in less adaptation, indicating that the capacity to learn a new strategy for localizing sound is more limited if the animals have previously adapted to conductive hearing loss in the opposite ear. Moreover, the degree of adaptation to the training stimulus for individual animals was significantly correlated with the extent to which learning extended to untrained octave band target sounds presented in silence and to broadband targets presented in background noise, suggesting that adaptation and generalization go hand in hand. Conclusions: Together, these findings provide further evidence for plasticity in the weighting of monaural and binaural cues during adaptation to unilateral conductive hearing loss, and show that the training-dependent recovery in spatial hearing can generalize to more naturalistic listening conditions, so long as the target sounds provide sufficient spatial information

A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair

The class IIa histone deacetylases (HDACs) have pivotal roles in the development of different tissues. Of this family, Schwann cells express Hdac4, 5 and 7 but not Hdac9. Here we show that a transcription factor regulated genetic compensatory mechanism within this family of proteins, blocks negative regulators of myelination ensuring peripheral nerve developmental myelination and remyelination after injury. Thus, when Hdac4 and 5 are knocked-out from Schwann cells in mice, a JUN-dependent mechanism induces the compensatory overexpression of Hdac7 permitting, although with a delay, the formation of the myelin sheath. When Hdac4,5 and 7 are simultaneously removed, the Myocyte-specific enhancer-factor d (MEF2D) binds to the promoter and induces the de novo expression of Hdac9, and although several melanocytic lineage genes are misexpressed and Remak bundle structure is disrupted, myelination proceeds after a long delay. Thus, our data unveil a finely tuned compensatory mechanism within the class IIa Hdac family, coordinated by distinct transcription factors, that guarantees the ability of Schwann cells to myelinate during development and remyelinate after nerve injury

Resonant Raman-active localized vibrational modes in AlyGa{1-y}NxAs{1-x} alloys: Experiment and firstprinciples calculations

The localized vibrational modes associated with substitutional aluminium and nitrogen atoms in AlyGa1−yNxAs1−x have been studied within first-principles density functional theory using a supercell approach. Localized vibrational modes related to N-AlmGa4−m (1≤m≥4) complexes have been identified, which reveal the formation of N-Al4 units well above random abundance, in qualitative agreement with a large calculated value (391 meV) of the Al-N bond formation energy. We determine the resonant Raman-active modes from the selection rule obtained by calculating the electron-phonon coupling strength and optical transition matrix elements and compare them with resonant Raman spectroscopy measurements. The localized modes from Raman scattering measurements with frequencies around 325, 385, 400, 450, 500, and 540 cm−1 are found to be in good agreement with the calculated modes (326, 364, 384, 410, 456, 507, and 556 cm−1). The modes are classified as follows: the two modes at 326 and 556 cm−1 belong to the N-AlGa3 configuration; there are three modes which belong to N-Al2Ga2 with frequencies at 326, 364, and 507 cm−1; the N-Al3Ga configuration gives rise to modes whose frequencies are 384 and 456 cm−1; and the mode at a frequency of 410 cm−1 belongs to the N-Al4 complex. The comparison of line intensities from samples before and after rapid thermal annealing allows us to experimentally distinguish vibrational modes associated with different clusters, in agreement with the theoretical assignments

Early dysfunction of functional connectivity in healthy elderly with subjective memory complaints

It is still an open question whether subjective memory complaints (SMC) can actually be considered to be clinically relevant predictors for the development of an objective memory impairment and even dementia. There is growing evidence that suggests that SMC are associated with an increased risk of dementia and with the presence of biological correlates of early Alzheimer's disease. In this paper, in order to shed some light on this issue, we try to discern whether subjects with SMC showed a different profile of functional connectivity compared with subjects with mild cognitive impairment (MCI) and healthy elderly subjects. In the present study, we compare the degree of synchronization of brain signals recorded with magnetoencephalography between three groups of subjects (56 in total): 19 with MCI, 12 with SMC and 25 healthy controls during a memory task. Synchronization likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. Briefly, results show that subjects with SMC have a very similar pattern of connectivity to control group, but on average, they present a lower synchronization value. These results could indicate that SMC are representing an initial stage with a hypo-synchronization (in comparison with the control group) where the brain system is still not compensating for the failing memory networks, but behaving as controls when compared with the MCI subjects

Assessing the coastal hazard of Medicane Ianos through ensemble modelling

On 18 September 2020, Medicane Ianos hit the western coast of Greece, resulting in flooding and severe damage at several coastal locations. In this work, we aim at evaluating its impact on sea conditions and the associated uncertainty through the use of an ensemble of numerical simulations. We applied a coupled wave–current model to an unstructured mesh, representing the whole Mediterranean Sea, with a grid resolution increasing in the Ionian Sea along the cyclone path and the landfall area. To investigate the uncertainty in modelling sea levels and waves for such an intense event, we performed an ensemble of ocean simulations using several coarse (10 km) and high-resolution (2 km) meteorological forcings from different mesoscale models. The performance of the ocean and wave models was evaluated against observations retrieved from fixed monitoring stations and satellites. All model runs emphasized the occurrence of severe sea conditions along the cyclone path and at the coast. Due to the rugged and complex coastline, extreme sea levels are localized at specific coastal sites. However, numerical results show a large spread of the simulated sea conditions for both the sea level and waves, highlighting the large uncertainty in simulating this kind of extreme event. The multi-model and multi-physics approach allows us to assess how the uncertainty propagates from meteorological to ocean variables and the subsequent coastal impact. The ensemble mean and standard deviation were combined to prove the hazard scenarios of the potential impact of such an extreme event to be used in a flood risk management plan.</p

Análisis de la acción tutorial en ingeniería y arquitectura. Gestión eficaz del tiempo

En este trabajo expondremos un análisis exhaustivo de como se ha desarrollado la acción tutorial en la Escuela Politécnica Superior de la Universidad de Alicante en el curso 2014/2015. El marcado carácter de voluntariedad de la acción tutorial en nuestro centro por parte de estudiantes y tutores permite que el trabajo se realice más satisfactoriamente tanto por parte de tutores como por parte de los estudiantes, puesto que han decidido seguir el plan por ello mismos y no como una imposición. Además expondremos nuestras experiencias en el desarrollo del Taller de Gestión Eficaz del Tiempo, taller desarrollado en nuestro centro bajo la tutela de la experta Nuria Alberquilla, que tiene entre otros muchos objetivos el aprendizaje y puesta en práctica de técnicas para realizar una gestión eficaz del tiempo, con un mejor equilibrio entre la vida académica y personal y la identificación de los principales factores externos e internos que influyen en los resultados obtenidos, y cómo mejorarlos

Experiencias en la tutorización de enseñanzas técnicas

El PAT en la Escuela Politécnica está abierto a todos aquellos tutores que deseen formar parte del plan y también a todos los alumnos, que, voluntariamente pueden marcar la opción de participar en el plan en la matrícula, y también a aquellos que, a pesar de no marcar la opción en la matrícula, finalmente han decidido seguir el plan de acción tutorial. Esta característica de participación e inscripción voluntaria permite que el trabajo se realice más satisfactoriamente tanto por parte de tutores como por parte de los alumnos, puesto que han decidido seguir el plan por ello mismos y no como una imposición. Con este trabajo nos proponemos presentar nuestras experiencias en el desarrollo de la tutorización de nuestros estudiantes así como la evolución en el desarrollo de la tutorización por pares