Metal dealing at the origin of the Chordata phylum: The metallothionein system and metal overload response in Amphioxus.

Non-vertebrate chordates, specifically amphioxus, are considered of the utmost interest for gaining insight into the evolutionary trends, i.e. differentiation and specialization, of gene/protein systems. In this work, MTs (metallothioneins), the most important metal binding proteins, are characterized for the first time in the cephalochordate subphylum at both gene and protein level, together with the main features defining the amphioxus response to cadmium and copper overload. Two MT genes (BfMT1 and BfMT2) have been identified in a contiguous region of the genome, as well as several ARE (antioxidant response element) and MRE (metal response element) located upstream the transcribed region. Their corresponding cDNAs exhibit identical sequence in the two lancelet species (B. floridae and B. lanceolatum), BfMT2 cDNA resulting from an alternative splicing event. BfMT1 is a polyvalent metal binding peptide that coordinates any of the studied metal ions (Zn, Cd or Cu) rendering complexes stable enough to last in physiological environments, which is fully concordant with the constitutive expression of its gene, and therefore, with a metal homeostasis housekeeping role. On the contrary, BfMT2 exhibits a clear ability to coordinate Cd(II) ions, while it is absolutely unable to fold into stable Cu (I) complexes, even as mixed species. This identifies it as an essential detoxification agent, which is consequently only induced in emergency situations. The cephalochordate MTs are not directly related to vertebrate MTs, neither by gene structure, protein similarity nor metal-binding behavior of the encoded peptides. The closest relative is the echinoderm MT, which confirm proposed phylogenetic relationships between these two groups. The current findings support the existence in most organisms of two types of MTs as for their metal binding preferences, devoted to different biological functions: multivalent MTs for housekeeping roles, and specialized MTs that evolve either as Cd-thioneins or Cu-thioneins, according to the ecophysiological needs of each kind of organisms.

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.

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

Multifunctional ligands for application in Alzheimer’s Disease: molecular modelling and biological evaluation

Projecte de recerca elaborat a partir d’una estada a la University of British Columbia, Canadà, entre 2010 i 2012 La malaltia d'Alzheimer (MA) representa avui la forma més comuna de demència en la població envellida. Malgrat fa 100 anys que va ser descoberta, encara avui no existeix cap tractament preventiu i/o curatiu ni cap agent de diagnòstic que permeti valorar quantitativament l'evolució d'aquesta malaltia. L'objectiu en el que s'emmarca aquest treball és contribuir a aportar solucions al problema de la manca d'agents terapèutics i de diagnosi, unívocs i rigorosos, per a la MA. Des del camp de la química bioinorgànica és fàcil fixar-se en l'excessiva concentració d'ions Zn(II) i Cu(II) en els cervells de malalts de MA, plantejar-se la seva utilització com a dianes terapèutica i, en conseqüència, cercar agents quelants que evitin la formació de plaques senils o contribueixin a la seva dissolució. Si bé aquest va ser el punt de partida d’aquest projecte, els múltiples factors implicats en la patogènesi de la MA fan que el clàssic paradigma d’ ¨una molècula, una diana¨ limiti la capacitat de la molècula de combatre aquesta malaltia tan complexa. Per tant, un esforç considerable s’ha dedicat al disseny d’agentsmultifuncionals que combatin els múltiples factors que caracteritzen el desenvolupament de la MA. En el present treball s’han dissenyat agents multifuncionals inspirats en dos esquelets moleculars ben establers i coneguts en el camp de la química medicinal: la tioflavina-T (ThT) i la deferiprona (DFP). La utilització de tècniques in silico que inclouen càlculs farmacocinètics i modelatge molecular ha estat un procés cabdal per a l’avaluació dels millors candidats en base als següents requeriments: (a) compliment de determinades propietats farmacocinètiques que estableixin el seu possible ús com a fàrmac (b) hidrofobicitat adequada per travessar la BBB i (c) interacció amb el pèptid Aen solució.

Behavioral Assumptions and Management Ability: A Tentative Test

The paper explores the consequences that relying on different behavioral assumptions in training managers may have on their future performance. We argue that training with an emphasis on the standard assumptions used in economics (rationality and self-interest) leads future managers to rely excessively on rational and explicit safeguarding, crowding out instinctive contractual heuristics and signaling a 'bad' type to potential partners. In contrast, human assumptions used in management theories, because of their diverse, implicit and even contradictory nature, do not conflict with the innate set of cooperative tools and may provide a good training ground for such tools. We present tentative confirmatory evidence by examining how the weight given to behavioral assumptions in the core courses of the top 100 business schools influences the average salaries of their MBA graduates. Controlling for the average quality of their students and some other schools' characteristics, average salaries are significantly greater for those schools whose core MBA courses contain a higher proportion of management courses as opposed to courses based on economics or technical disciplines.

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.

One person in the battlefield is not a warrior: Self-construal, perceived ability to make a difference, and socially responsible behavior

We suggest that cultivating an individual's connectedness to others promotes sociallyresponsible behavior both directly and indirectly through increased perceived abilityto make a difference. Individuals whose interdependent self is more prominent feel theyhave more of an impact on larger scale societal outcomes and, therefore, engage more insocially responsible behaviors than do individuals whose independent self is moreprominent. We test these hypotheses in two experiments in which participants makefinancial contributions or exert an effort for a social cause. In a survey, we find thatperceived effectiveness mediates the effect of self-construal on socially responsibleconsumption.

The organization of research corporations and researcher ability

This paper analyzes the formation of Research Corporations as an alternative governance structure for performing R&D compared to pursuing in-house R&D projects. Research Corporations are privatefor-profit research centers that bring together several firms with similar research goals. In a Research Corporation formal authority over the choice of projects is jointly exercised by the top management of the member firms. A private for-profit organization cannot commit not to interfere with the project choice of the researchers. However, increasing the number of member firms of the Research Corporation reduces the incentive of member firms to meddle with the research projects of researchers because exercising formal authority over the choice of research projects is a public good. The Research Corporation thus offers researchers greater autonomy than a single firm pursuing an identical research program in its in-house R&D department. This attracts higher ability researchers to the Research Corporation compared to the internal R&D department. The paper uses the theoretical model to analyze the organization of the Microelectronics and Computer Technology Corporation (MCC). The facts of this case confirm the existence of a tension between control over the choice of research projects and the ability of researchers that the organization is able to attract or hold onto.

Behavioral assumptions and management ability

The paper explores the consequences that relying on different behavioral assumptions intraining managers may have on their future performance. We argue that training with anemphasis on the standard assumptions used in economics (rationality and self-interest) is goodfor technical posts but may also lead future managers to rely excessively on rational and explicitsafeguarding, crowding out instinctive relational heuristics and signaling a bad human type topotential partners. In contrast, human assumptions used in management theories, because oftheir diverse, implicit and even contradictory nature, do not conflict with the innate set ofcooperative tools and may provide a good training ground for such tools. We present tentativeconfirmatory evidence by examining how the weight given to behavioral assumptions in the corecourses of the top 100 business schools influences the average salaries of their MBA graduates.Controlling for the self-selected average quality of their students and some other schools characteristics, average salaries are seen to be significantly greater for schools whose core MBAcourses contain a higher proportion of management courses as opposed to courses based oneconomics or technical disciplines.

Predictive ability of severe rainfall events over Catalonia for the year 2008

This paper analyses the predictive ability of quantitative precipitation forecasts (QPF) and the so-called "poor-man" rainfall probabilistic forecasts (RPF). With this aim, the full set of warnings issued by the Meteorological Service of Catalonia (SMC) for potentially-dangerous events due to severe precipitation has been analysed for the year 2008. For each of the 37 warnings, the QPFs obtained from the limited-area model MM5 have been verified against hourly precipitation data provided by the rain gauge network covering Catalonia (NE of Spain), managed by SMC. For a group of five selected case studies, a QPF comparison has been undertaken between the MM5 and COSMO-I7 limited-area models. Although MM5's predictive ability has been examined for these five cases by making use of satellite data, this paper only shows in detail the heavy precipitation event on the 9¿10 May 2008. Finally, the "poor-man" rainfall probabilistic forecasts (RPF) issued by SMC at regional scale have also been tested against hourly precipitation observations. Verification results show that for long events (>24 h) MM5 tends to overestimate total precipitation, whereas for short events (¿24 h) the model tends instead to underestimate precipitation. The analysis of the five case studies concludes that most of MM5's QPF errors are mainly triggered by very poor representation of some of its cloud microphysical species, particularly the cloud liquid water and, to a lesser degree, the water vapor. The models' performance comparison demonstrates that MM5 and COSMO-I7 are on the same level of QPF skill, at least for the intense-rainfall events dealt with in the five case studies, whilst the warnings based on RPF issued by SMC have proven fairly correct when tested against hourly observed precipitation for 6-h intervals and at a small region scale. Throughout this study, we have only dealt with (SMC-issued) warning episodes in order to analyse deterministic (MM5 and COSMO-I7) and probabilistic (SMC) rainfall forecasts; therefore we have not taken into account those episodes that might (or might not) have been missed by the official SMC warnings. Therefore, whenever we talk about "misses", it is always in relation to the deterministic LAMs' QPFs.

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.

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.