Target-guided synthesis of metal-based phosphatase inhibitors

Report for the scientific sojourn at the Imperial College of London, United Kingdom, from 2007 to 2009. PTEN is a tumour suppressor enzyme that plays important roles in the PI3K pathway which regulates growth, proliferation and survival and is thus related to many human disorders such as diabetes, neurodegenerative diseases, cardiovascular complications and cancer. It is hence of great interest to understand in detail its molecular behaviour and to find small molecules that can switch on/off its activity. For this purpose, metal complexes have been synthesized and preliminary studies in vivo show that all are capable of inhibiting PTEN.

Hemilabile phosphine ligands in molybdenum and tungsten octahedral environments

The synthesis of three bidentate, hemilabile phosphine ligands, newly synthesized in the research group (TPOdiphos, DPPrPOdiphos and SODPdiphos), has been up-scaled and optimized. The ligand substitution reaction on Mo(CO)6 and W(CO)6 has been studied and the corresponding complexes fac-[MTPOdiphos(CO)3], fac-[MDPPrPOdiphos(CO)3], and fac-[MSODPdiphos(CO)3], (M= Mo, W) have been isolated in good yields and characterized by NMR, IR and HR MS. In the case of fac- [MoTPOdiphos(CO)3] the XRD crystal structure was resolved. The complexes were found to be octahedral, neutral molecules, with the metal in the zero oxidation state and the ligand adopting a facial P,P,O-coordination. The hard ligand atom (oxygen) is expected to exhibit special features the future applications of these novel ligands.

Full Exploration of the Diels–Alder Cycloaddition on Metallofullerenes M3N@C80 (M=Sc, Lu, Gd): The D5h versus Ih Isomer and the Influence of the Metal Cluster

In this work a detailed investigation of the exohedral reactivity of the most important and abundant endohedral metallofullerene (EMF) is provided, that is, Sc3N@Ih-C80 and its D5h counterpart Sc3N@D5h-C80, and the (bio)chemically relevant lutetium- and gadolinium-based M3N@Ih/D5h-C80 EMFs (M=Sc, Lu, Gd). In particular, we analyze the thermodynamics and kinetics of the Diels–Alder cycloaddition of s-cis-1,3-butadiene on all the different bonds of the Ih-C80 and D5h-C80 cages and their endohedral derivatives. First, we discuss the thermodynamic and kinetic aspects of the cycloaddition reaction on the hollow fullerenes and the two isomers of Sc3N@C80. Afterwards, the effect of the nature of the metal nitride is analyzed in detail. In general, our BP86/TZP//BP86/DZP calculations indicate that [5,6] bonds are more reactive than [6,6] bonds for the two isomers. The [5,6] bond D5h-b, which is the most similar to the unique [5,6] bond type in the icosahedral cage, Ih-a, is the most reactive bond in M3N@D5h-C80 regardless of M. Sc3N@C80 and Lu3N@C80 give similar results; the regioselectivity is, however, significantly reduced for the larger and more electropositive M=Gd, as previously found in similar metallofullerenes. Calculations also show that the D5h isomer is more reactive from the kinetic point of view than the Ih one in all cases which is in good agreement with experiments

Oxidation of silicon: further tests for the interfacial silicon emission model

The classical description of Si oxidation given by Deal and Grove has well-known limitations for thin oxides (below 200 Ã). Among the large number of alternative models published so far, the interfacial emission model has shown the greatest ability to fit the experimental oxidation curves. It relies on the assumption that during oxidation Si interstitials are emitted to the oxide to release strain and that the accumulation of these interstitials near the interface reduces the reaction rate there. The resulting set of differential equations makes it possible to model diverse oxidation experiments. In this paper, we have compared its predictions with two sets of experiments: (1) the pressure dependence for subatmospheric oxygen pressure and (2) the enhancement of the oxidation rate after annealing in inert atmosphere. The result is not satisfactory and raises serious doubts about the model’s correctness

Sonidos del metal : el bombardino en las formaciones de viento metal

Este proyecto tiene como objetivo el estudio de la relación que el bombardino tiene con las formaciones más importantes de viento metal. Para ello he creído necesario, antes de profundizar en este tema, dar a conocer su historia y evolución. Mi intención con este proyecto es contribuir al enriquecimiento del patrimonio de este maravilloso instrumento, que poco a poco, va ganando el respeto que se merece.

Fábrica de "Metalheads" : arquetipo de la representación del aficionado al Heavy Metal en España

El presente estudio expone los resultados del tema desarrollado en la línea investigativa de culturas urbanas contemporáneas y procesos comunicacionales. Trabajo que describe (construye) el arquetipo del aficionado al heavy metal en España.

Mitochondrial Fatty Acid Oxidation in Obesity

Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders. Antioxid. Redox Signal. 00, 000000.

Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate

FSP27 (CIDEC in humans) is a protein associated with lipid droplets that downregulates the fatty acid oxidation (FAO) rate when it is overexpressed. However, little is known about its physiological role in liver. Here, we show that fasting regulates liver expression of Fsp27 in a time-dependent manner. Thus, during the initial stages of fasting a maximal induction of 800-fold was achieved, while during the later phase of fasting, Fsp27 expression decreased. The early response to fasting can be explained by a canonical PKA-CREB-CRTC2 signaling pathway since: i) CIDEC expression was induced by forskolin, ii) Fsp27 promoter activity was increased by CREB, and iii) Fsp27 expression was upregulated in the liver of Sirt1 knockout animals. Interestingly, pharmacological (etomoxir) or genetic (Hmgcs2 interference) inhibition of the FAO rate increases the in vivo expression of Fsp27 during fasting. Similarly, CIDEC expression was upregulated in HepG2 cells by either etomoxir or HMGCS2 interference. Our data indicate that there is a kinetic mechanism of auto-regulation between short- and long-term fasting, by which free fatty acids delivered to the liver during early fasting are accumulated/exported by FSP27/CIDEC, while over longer periods of fasting they are degraded in the mitochondria through the carnitine palmitoyl transferase (CPT) system.

Role of fluid mixing in deep dissolution of carbonates

The presence of cavities filled with new minerals in carbonate rocks is a common feature in oil reservoirs and lead-zinc deposits. Since groundwater equilibrates rapidly with carbonates, the presence of dissolution cavities in deep carbonate host rocks is a paradox. Two alternative geochemical processes have been proposed to dissolve carbonates at depth: hydrogen sulfide oxidation to sulfuric acid, and metal sulfide precipitation. With the aid of geochemical modeling we show that mixing two warm solutions saturated with carbonate results in a new solution that dissolves limestone. Variations in the proportion of the end-member fluids can also form a supersaturated mixture and fill the cavity with a new generation of carbonate. Mixing is in general more effective in dissolving carbonates than the aforementioned processes. Moreover, mixing is consistent with the wide set of textures and mineral proportions observed in cavity infillings.

Unipolar transport and shot noise in metal-semiconductor-metal structures

We carry out a self-consistent analytical theory of unipolar current and noise properties of metal-semiconductor-metal structures made of highly resistive semiconductors in the presence of an applied bias of arbitrary strength. By including the effects of the diffusion current we succeed in studying the whole range of carrier injection conditions going from low level injection, where the structure behaves as a linear resistor, to high level injection, where the structure behaves as a space charge limited diode. We show that these structures display shot noise at the highest voltages. Remarkably the crossover from Nyquist noise to shot noise exhibits a complicated behavior with increasing current where an initial square root dependence (double thermal noise) is followed by a cubic power law.

Conduction mechanisms and charge storage in Si-nanocrystals metal-oxide-semiconductor memory devices studied with conducting atomic force microscopy

In this work, we demonstrate that conductive atomic force microscopy (C-AFM) is a very powerful tool to investigate, at the nanoscale, metal-oxide-semiconductor structures with silicon nanocrystals (Si-nc) embedded in the gate oxide as memory devices. The high lateral resolution of this technique allows us to study extremely small areas ( ~ 300nm2) and, therefore, the electrical properties of a reduced number of Si-nc. C-AFM experiments have demonstrated that Si-nc enhance the gate oxide electrical conduction due to trap-assisted tunneling. On the other hand, Si-nc can act as trapping centers. The amount of charge stored in Si-nc has been estimated through the change induced in the barrier height measured from the I-V characteristics. The results show that only ~ 20% of the Si-nc are charged, demonstrating that the electrical behavior at the nanoscale is consistent with the macroscopic characterization.

X-ray photoelectron spectroscopy analysis of ion¿beam¿induced oxidation of GaAs and AlGaAs

The oxidation of GaAs and AlGaAs targets subjected to O2+ bombardment has been analyzed, using in situ x¿ray photoelectron spectroscopy, as a function of time until steady state is reached. The oxides formed by the O2+ bombardment have been characterized in terms of composition and binding energy. A strong energy and angular dependence for the oxidation of As relative to Ga is found. Low energies as well as near normal angles of incidence favor the oxidation of As. The difference between Ga and As can be explained in terms of the formation enthalpy for the oxide and the excess supply of oxygen. In an AlGaAs target the Al is very quickly completely oxidized irrespective of the experimental conditions. The steady state composition of the altered layers show in all cases a preferential removal of As.

Modifications in the Si valence band after ion-beam-induced oxidation

The changes undergone by the Si surface after oxygen bombardment have special interest for acquiring a good understanding of the Si+-ion emission during secondary ion mass spectrometry (SIMS) analysis. For this reason a detailed investigation on the stoichiometry of the builtup surface oxides has been carried out using in situ x-ray photoemission spectroscopy (XPS). The XPS analysis of the Si 2p core level indicates a strong presence of suboxide chemical states when bombarding at angles of incidence larger than 30°. In this work a special emphasis on the analysis and interpretation of the valence band region was made. Since the surface stoichiometry or degree of oxidation varies with the angle of incidence, the respective valence band structures also differ. A comparison with experimentally measured and theoretically derived Si valence band and SiO2 valence band suggests that the new valence bands are formed by a combination of these two. This arises from the fact that Si¿Si bonds are present on the Si¿suboxide molecules, and therefore the corresponding 3p-3p Si-like subband, which extends towards the Si Fermi level, forms the top of the respective new valence bands. Small variations in intensity and energy position for this subband have drastic implications on the intensity of the Si+-ion emission during sputtering in SIMS measurements. A model combining chemically enhanced emission and resonant tunneling effects is suggested for the variations observed in ion emission during O+2 bombardment for Si targets.

Metal-Nitride-oxide-semiconductor light-emitting devices for general lighting.

The potential for application of silicon nitride-based light sources to general lighting is reported. The mechanism of current injection and transport in silicon nitride layers and silicon oxide tunnel layers is determined by electro-optical characterization of both bi- and tri-layers. It is shown that red luminescence is due to bipolar injection by direct tunneling, whereas Poole-Frenkel ionization is responsible for blue-green emission. The emission appears warm white to the eye, and the technology has potential for large-area lighting devices. A photometric study, including color rendering, color quality and luminous efficacy of radiation, measured under various AC excitation conditions, is given for a spectrum deemed promising for lighting. A correlated color temperature of 4800K was obtained using a 35% duty cycle of the AC excitation signal. Under these conditions, values for general color rendering index of 93 and luminous efficacy of radiation of 112 lm/W are demonstrated. This proof of concept demonstrates that mature silicon technology, which is extendable to lowcost, large-area lamps, can be used for general lighting purposes. Once the external quantum efficiency is improved to exceed 10%, this technique could be competitive with other energy-efficient solid-state lighting options. ©2011 Optical Society of America OCIS codes: (230.2090) Electro-optical devices; (150.2950) Illumination.

The effects of electron-hole separation on the photoconductivity of individual metal oxide nanowires

The responses of individual ZnO nanowires to UV light demonstrate that the persistent photoconductivity (PPC) state is directly related to the electron¿hole separation near the surface. Our results demonstrate that the electrical transport in these nanomaterials is influenced by the surface in two different ways. On the one hand, the effective mobility and the density of free carriers are determined by recombination mechanisms assisted by the oxidizing molecules in air. This phenomenon can also be blocked by surface passivation. On the other hand, the surface built-in potential separates the photogenerated electron¿hole pairs and accumulates holes at the surface. After illumination, the charge separation makes the electron¿hole recombination difficult and originates PPC. This effect is quickly reverted after increasing either the probing current (self-heating by Joule dissipation) or the oxygen content in air (favouring the surface recombination mechanisms). The model for PPC in individual nanowires presented here illustrates the intrinsic potential of metal oxide nanowires to develop optoelectronic devices or optochemical sensors with better and new performances.