Pharmacokinetic aspects of Tert-Butylaminoethyl disulfide, an experimental drug against schistosomiasis in mice

A preliminary study of the pharmacokinetic parameters of t-Butylaminoethyl disulfide was performed after administration of two different single doses (35 and 300 mg/kg) of either the cold or labelled drug. Plasma or blood samples were treated with dithiothreitol, perchloric acid, and, after filtration, submitted to further purification with anionic resein. In the final step, the drug was retained on a cationic resin column, eluted with NaCl 1M and detected according to the method of Ellman (1958). Alternatively, radioactive drug was detected by liquid scintillation counting. The results corresponding to the smaller dose of total drug suggested a pharmacokinetic behavior related to a one open compartment model with the following parameters: area under the intravenous curve (AUC i.v.):671 ± 14; AUC oral: 150 ± 40 µg.min. ml [raised to the power of -1]; elimination rate constant: 0.071 min [raised to the power of -1]; biological half life: 9.8 min; distribution volume: 0.74 ml/g. For the higher dose, the results seemed to obey a more complex undertermined model. Combining the results, the occurence of a dose-dependent pharmacokinetic behavior is suggested, the drug being rapidly absorbed and rapidly eliminated; the elimination process being related mainly to metabolization. The drug seems to be more toxic when administered I.V. because by this route it escapes first pass metabolism, while being quickly distributed to tissues. The maximum tolerated blood level seems to be around 16 µg/ml.

Miniaturización de componentes planares de microondas mediante técnicas basadas en metamateriales: aplicación a un desfasador de cuadratura

En este trabajo se describe la miniaturización del diseño de un desfasador de cuadratura mediante líneas de transmisión metamaterial en tecnología microstrip. Para conseguir la miniaturización del diseño se utiliza la topología Spiral Resonator (SR). Los desfasadores de cuadratura han sido diseñados, fabricados y medidos. Mediante este proceso se ha consiguido un dispositivo metamaterial que presenta una reducción de un 77% del tamaño respecto a las líneas convencionales.

Diseño de inversores de impedancias de microondas compactos basados en metamateriales: aplicación a divisores de potencia

Recientemente ha surgido un nuevo campo de investigación en el área del electromagnetismo aplicado y de la ingeniería de microondas, basado en el control de las propiedades electromagnéticas de estructuras artificiales, conocidas como metamateriales. El objetivo principal de este proyecto es el estudio y control del comportamiento de estas estructuras artificiales, y su posterior aplicación para la síntesis de dispositivos compactos de microondas. En el primer capítulo se hace una introducción a los metamateriales en la que se exponen sus principales propiedades electromagnéticas, para finalmente presentar las líneas de transmisión zurdas que se suelen utilizar en el diseño de metamateriales. En el segundo capítulo se realiza un estudio de las propiedades y del funcionamiento de una celda metamaterial. Finalmente en el tercer capítulo se exponen diferentes dispositivos diseñados mediante la utilización de este tipo de celdas.

Monitor EMG con conexión inalámbrica

El sistema desarrollado en este trabajo permite la detección de fatiga del músculo de un paciente. Las señales electromiográficas generadas por el músculo son detectadas mediante electrodos superficiales, que sirven de entrada al circuito hacia los diferentes canales de entrada. Tras una primera etapa de amplificación, las señales son filtradas por un filtro pasabanda. Las señales acondicionadas se digitalizan mediante un conversor analógico digital que está conectado a un microcontrolador. Éste establece la comunicación con el PC enviándole los datos a través del puerto serie. Finalmente, mediante un programa implementado en Labview se procesan los datos y se determina la existencia o no de fatiga muscular.

Disseny d'un sistema HW/SW de control remot amb dispositius FPGA

El projecte que es presenta a continuació, té com a objectiu implementar un sistema HW/SW encastat en una FPGA, capaç d’executar funcions de control remot per infraroig en plataformes de televisió flexibles de Sony Corp. El disseny obtingut, s’incorporarà a un sistema més ampli de verificació i test de circuits impresos, dins del marc de producció SMD. La finalitat d’aquest projecte, és la realització d’un sistema flexible per a la implementació de comandaments de comunicació per infraroig amb circuits impresos. Prèviament, s’ha estudiat els conceptes bàsics referents a la implementació de sistemes amb FPGAs, la seva metodologia de desenvolupament i les principals característiques de la seva arquitectura. Com a especificacions, s’ha utilitzat l’estàndard de control remot per infraroig de Sony Corp SIRCS (Sony Infrared remote control system).

Neuroscience, quantum indeterminism and the Cartesian soul.

Quantum indeterminism is frequently invoked as a solution to the problem of how a disembodied soul might interact with the brain (as Descartes proposed), and is sometimes invoked in theories of libertarian free will even when they do not involve dualistic assumptions. Taking as example the Eccles-Beck model of interaction between self (or soul) and brain at the level of synaptic exocytosis, I here evaluate the plausibility of these approaches. I conclude that Heisenbergian uncertainty is too small to affect synaptic function, and that amplification by chaos or by other means does not provide a solution to this problem. Furthermore, even if Heisenbergian effects did modify brain functioning, the changes would be swamped by those due to thermal noise. Cells and neural circuits have powerful noise-resistance mechanisms, that are adequate protection against thermal noise and must therefore be more than sufficient to buffer against Heisenbergian effects. Other forms of quantum indeterminism must be considered, because these can be much greater than Heisenbergian uncertainty, but these have not so far been shown to play a role in the brain.

Pathological substrates of cognitive decline in Alzheimer's disease

The progressive development of Alzheimer's disease (AD)-related lesions such as neurofibrillary tangles,amyloid deposits and synaptic loss within the cerebral cortex is a main event of brain aging.Recent neuropathologic studies strongly suggested that the clinical diagnosis of dementia depends more on the severity and topography of pathologic changes than on the presence of a qualitative marker. However, several methodological problems such as selection biases, case-control design,density-based measures, and masking effects of concomitant pathologies should be taken into account when interpreting these data. In last years, the use of stereologic counting permitted to define reliably the cognitive impact of AD lesions in the human brain. Unlike fibrillar amyloid deposits that are poorly or not related to the dementia severity, the use of this method documented that total neurofibrillary tangles and neuron numbers in the CA1 field are the best correlates of cognitive deterioration in brain aging. Loss of dendritic spines in neocortical but not hippocampal areas has a modest but independent contribution to dementia. In contrast, the importance of early dendritic and axonal tau-related pathologic changes such as neuropil threads remains doubtful. Despite these progresses, neuronal pathology and synaptic loss in cases with pure AD pathology cannot explain more than 50% of clinical severity. The present review discusses the complex structure/function relationships in brain aging and AD within the theoretical framework of the functional neuropathology of brain aging.

Purification and activity standardisation of a (166m)Ho solution.

As part of a project to use the long-lived (T(1/2)=1200a) (166m)Ho as reference source in its reference ionisation chamber, IRA standardised a commercially acquired solution of this nuclide using the 4pibeta-gamma coincidence and 4pigamma (NaI) methods. The (166m)Ho solution supplied by Isotope Product Laboratories was measured to have about 5% Europium impurities (3% (154)Eu, 0.94% (152)Eu and 0.9% (155)Eu). Holmium had therefore to be separated from europium, and this was carried out by means of ion-exchange chromatography. The holmium fractions were collected without europium contamination: 162h long HPGe gamma measurements indicated no europium impurity (detection limits of 0.01% for (152)Eu and (154)Eu, and 0.03% for (155)Eu). The primary measurement of the purified (166m)Ho solution with the 4pi (PC) beta-gamma coincidence technique was carried out at three gamma energy settings: a window around the 184.4keV peak and gamma thresholds at 121.8 and 637.3keV. The results show very good self-consistency, and the activity concentration of the solution was evaluated to be 45.640+/-0.098kBq/g (0.21% with k=1). The activity concentration of this solution was also measured by integral counting with a well-type 5''x5'' NaI(Tl) detector and efficiencies computed by Monte Carlo simulations using the GEANT code. These measurements were mutually consistent, while the resulting weighted average of the 4pi NaI(Tl) method was found to agree within 0.15% with the result of the 4pibeta-gamma coincidence technique. An ampoule of this solution and the measured value of the concentration were submitted to the BIPM as a contribution to the Système International de Référence.

Complementary function and integrated wiring of the evolutionarily distinct Drosophila olfactory subsystems.

To sense myriad environmental odors, animals have evolved multiple, large families of divergent olfactory receptors. How and why distinct receptor repertoires and their associated circuits are functionally and anatomically integrated is essentially unknown. We have addressed these questions through comprehensive comparative analysis of the Drosophila olfactory subsystems that express the ionotropic receptors (IRs) and odorant receptors (ORs). We identify ligands for most IR neuron classes, revealing their specificity for select amines and acids, which complements the broader tuning of ORs for esters and alcohols. IR and OR sensory neurons exhibit glomerular convergence in segregated, although interconnected, zones of the primary olfactory center, but these circuits are extensively interdigitated in higher brain regions. Consistently, behavioral responses to odors arise from an interplay between IR- and OR-dependent pathways. We integrate knowledge on the different phylogenetic and developmental properties of these receptors and circuits to propose models for the functional contributions and evolution of these distinct olfactory subsystems.

Disseny i caracterització d'estructures RF amb printed electronics per a RFID

En els últims anys printed electronics està aixecant un gran interès entre la indústria electrònica. Aquest tipus de procés consisteix en imprimir circuits amb tècniques d'impressió convencionals utilitzant tintes conductores, resistives, dielèctriques o semiconductores sobre substrats flexibles de baix cost com paper o plàstic. Fer servir aquestes tècniques s'espera que suposi una reducció dels costos de producció degut a que és un procés totalment additiu el que fa que sigui més senzill i es redueixi la quantitat de material emprat. El disseny de dispositius bàsics com resistències, condensadors i bobines per posteriorment veure la relació entre simulacions i valors obtinguts ha ocupat la primera part del projecte. La segona s’ha centrat en fer prototips d’antenes per a RFID (Radio Frequency IDentification) amb la tecnologia que es disposa a CEPHIS (Centre de Prototips i Solucions Hardwre-Software). Tot això ha servit per caracteritzar la tecnologia de la que es disposa i saber en quins apartats s’ha de seguir treballant per aconseguir millors prestacions.

Disseny i implementació d'una etapa d'acondicionament per a mesures de conductivitat realitzades amb un microscopi de forces atòmiques

En aquest treball, s’ha dissenyat un mòdul d’acondicionament a fi de millorar les mesures de conductivitat realitzades amb un AFM (Microscopi de Forces Atòmiques). L’equip actual disposa d’un preamplificador de baix soroll amb un guany de 10 10V/A. Donat que els corrents que es pretenen mesurar són extremadament petits (~pA), s’ha dissenyat un filtre per eliminar diferents fonts de soroll, com ara el soroll que introdueix la xarxa elèctrica a 50Hz. Es pretén reduir aquesta component freqüencial un factor mínim de 10 (20dB). També s’ha afegit un filtre passa baixos per eliminar els soroll que es troba fora de l’amplada de banda del preamplificador. S’ha introduït una etapa d’amplificació de guany variable: 1, 10 i 100 per augmentar la flexibilitat de l’equip i finalment també s’ha dissenyat una etapa per eliminar la tensió d’offset d’aquest amplificador. L’abast del treball anirà des del disseny fins la implementació final sobre una placa PCB.

Fitxers de microdades a la Biblioteca de la UPF

Experiència sobre la identificació, la compilació i la posada a disposició dels usuaris dels recursos estadístics de temàtica social i econòmica utilitzats pels investigadors de la UPF. Es va fer un estudi d'identificació dels recursos utilitzats, de la seva procedència i de la font de finançament. Davant dels resultats es van iniciar dues línies d'actuació segons si les dades estadístiques eren d'accés lliure o de consulta restringida. Pel que fa als fitxers d'accés lliure, es va procedir a la instal·lació, conjuntament amb el Servei d’informàtica, dels fitxers en un servidor i possibilitar-ne l’accessibilitat a través de la xarxa UPF, es va elaborar una guia de desenvolupament de la col·lecció per aquests materials, per tal d’equilibrar el fons i respondre a les necessitats dels usuaris i es van fer diverses accions per millorar la recuperació del material a través del web i del catàleg de la Biblioteca. Pel que fa a les microdades van ser tractades apart tenint en compte les característiques especials d’aquest material, protegit per les lleis de protecció de dades personals. Es va crear una xarxa interna amb un sistema d’accés i control d’usuaris molt estricte, amb la col·laboració del Servei d’Informàtica, es va elaborar un circuit d'adquisició (amb negociacions amb les agències productores per signar llicències institucionals) i gestió interna dels materials. En conclusió: la Biblioteca, amb un actitud proactiva, es va anticipar a les necessitats dels investigadors i va donar-los resposta, tot va millorant la gestió i l'accessibilitat d'uns recursos -fitxers estadístics- tradicionalment molt restringits i racionalitzant processos i circuits.

Imaging of experience-dependent structural plasticity in the mouse neocortex in vivo

The functionality of adult neocortical circuits can be altered by novel experiences or learning. This functional plasticity appears to rely on changes in the strength of neuronal connections that were established during development. Here we will describe some of our studies in which we have addressed whether structural changes, including the remodeling of axons and dendrites with synapse formation and elimination, could underlie experience-dependent plasticity in the adult neocortex. Using 2-photon laser-scanning microscopes and transgenic mice expressing GFP in a subset of pyramidal cells, we have observed that a small subset of dendritic spines continuously appear and disappear on a daily basis, whereas the majority of spines persists for months. Axonal boutons from different neuronal classes displayed similar behavior, although the extent of remodeling varied. Under baseline conditions, new spines in the barrel cortex were mostly transient and rarely survived for more than a week. However, when every other whisker was trimmed, the generation and loss of persistent spines was enhanced. Ultrastructural reconstruction of previously imaged spines and boutons showed that new spines slowly form synapses. New spines persisting for a few days always had synapses, whereas very young spines often lacked synapses. New synapses were predominantly found on large, multi-synapse boutons, suggesting that spine growth is followed by synapse formation, preferentially on existing boutons. Altogether our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons and promotes the formation of new synapses. These synaptic changes likely underlie experience-dependent functional remodeling of specific neocortical circuits.

Neuropathological substrates and structural changes in late-life depression: the impact of vascular burden.

A first episode of depression after 65 years of age has long been associated with both severe macrovascular and small microvascular pathology. Among the three more frequent forms of depression in old age, post-stroke depression has been associated with an abrupt damage of cortical circuits involved in monoamine production and mood regulation. Late-onset depression (LOD) in the absence of stroke has been related to lacunes and white matter lesions that invade both the neocortex and subcortical nuclei. Recurrent late-life depression is thought to induce neuronal loss in the hippocampal formation and white matter lesions that affect limbic pathways. Despite an impressive number of magnetic resonance imaging (MRI) studies in this field, the presence of a causal relationship between structural changes in the human brain and LOD is still controversial. The present article provides a critical overview of the contribution of neuropathology in post-stroke, late-onset, and late-life recurrent depression. Recent autopsy findings challenge the role of stroke location in the occurrence of post-stroke depression by pointing to the deleterious effect of subcortical lacunes. Despite the lines of evidences supporting the association between MRI-assessed white matter changes and mood dysregulation, lacunes, periventricular and deep white matter demyelination are all unrelated to the occurrence of LOD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of aging-related neurodegenerative changes in the human brain. However, they also provide data in favor of the neurotoxic theory of depression by showing that neuronal loss occurs in the hippocampus of chronically depressed patients. These three paradigms are discussed in the light of the complex relationships between psychosocial determinants and biological vulnerability in affective disorders.