Sintesi di nuovi ligandi della Glicoproteina-P a struttura Ariletilanilinica per lo sviluppo di traccianti per la PET

Le ATP-binding cassette transporters (trasportatori ABC),fanno parte di una superfamiglia proteica molto diffusa in diversi tipi di organismi: dai procarioti all’uomo. In quest’ultimo,derivano dall’espressione di 49 geni dai quali si originano ben 7 sottoclassi : ABC-A G. Sono proteine transmembrana,che sono in grado di regolare il passaggio di diverse tipologie di sostanze attraverso queste barriere. Per poter svolgere tale funzione, necessitano di una fonte energetica,la quale è costituita dall’ATP (adenosina trifosfato) e dalla sua successiva idrolisi. Per questo motivo,questi trasportatori sono,a tutti gli effetti,delle “pompe di membrana”. Possiamo,inoltre,operare una loro suddivisione anche in base alla direzione secondo la quale le sostanze vengono trasportate,abbiamo : • Importatori • Esportatori/Efflussori Gli Importatori sono presenti solo nei Procarioti. Invece,negli Eucarioti,si riscontra la esclusiva presenza degli Esportatori. Quest’ultimi,esercitano una funzione protettiva contrastando l’accumulo di moltissime tipologie di sostanze potenzialmente pericolose o per un determinato distretto fisiologico o per la sopravvivenza della singola cellula. Ne consegue che posseggano la capacità di interagire con una vasta gamma di substrati,strutturalmente e funzionalmente,molto diversi fra loro : dai metaboliti ai lipidi,dagli steroli ai farmaci. Grazie a questa capacità,si riscontra la loro presenza all’interno di numerosissime membrane di diversi distretti biologici,come : -Barriera Emato-Encefalica (BEE) -Placenta -Intestino -Stomaco -Fegato Essendo proteine trasportatrici,è pacifico che influenzino o siano coinvolte direttamente anche nella regolazione di molti processi cellulari. Questo ha fatto sì che,col tempo,siano state sempre di più oggetto di studi e ricerca. Fra queste, particolare interesse,lo ha suscitato la ABC-B1,altresì nota come Glicoproteina-P (P-gp),soprattutto a causa del suo ruolo in alcune patologie neuro-degenerative (Parkinson,Alzheimer) e tumorali. In questo senso,l’aspetto sul quale la ricerca si sta concentrando negli ultimi anni,è,oltre alla caratterizzazione delle sue funzioni e della sua struttura,la valutazione della sua espressione in condizioni normali e patologiche. Potenzialmente,potrebbe rappresentare uno dei bersagli principali,sia per quanto riguarda la diagnosi che il trattamento,di tali patologie. I vantaggi,teorici,che si potrebbero riscontrare sono svariati e riguardano : la maggiore capacità di diagnosi delle patologie,l’aumento della biodisponibilità dei farmaci,i migliori risultati terapeutici,la riduzione delle dosi,la riduzione della probabilità che insorgano effetti collaterali e fenomeni di resistenza ai farmaci,l’aumento della qualità di vita dei pazienti e la riduzione della spesa farmaceutic

Critique [of Institutional Racism]

As Deloria indicates in the opening lines of his essay, the dominant paradigm of racism in the 1960s reflected the popularly held belief that racism was an individual phenomena. Consequently. if racist individuals were confronted and curtailed or converted, the argument concluded, then discrimination would come to an end. However, history has shown us that we can have racist institutions without having racist individuals. For instance, our education institutions perpetuate racial, as well as sex, inequality. Yet it is possible for every member of such an institution to be non-racist, as well as non-sexist

The Hollow Promise of an Accounting Standard Setter

Purpose – This paper applies a power framework to critically analyse the international accounting standard setting process for the extractive industries. Design/methodology/approach – Publicly available data, including comment letters, annual reports, company websites, and IASC/IASB pronouncements, is used to make connections between the key plays involved in the international accounting standard setting process for the extractive industries. Findings – Lukes’ (1974) conception of power is used to explain the community of interests that developed between the IASC/IASB and extractive industries constituents. This community of interests is shown to have enabled the extractive industries to mobilise its power to paralyse the standard setting body and secure favourable regulation. While the politicisation of accounting standard setting is widely acknowledged, the revelation that economically dominant groups can covertly wield such power is a sobering one in the light of the worldwide promotion and adoption of International Financial Reporting Standards. Originality/value – This paper contributes to understanding of the presence of power in the international accounting standard setting process and how it is mobilised by key constituents

The Herschel Virgo Cluster Survey - II. Truncated dust disks in H I-deficient spirals

By combining Herschel-SPIRE observations obtained as part of the Herschel Virgo Cluster Survey with 21 cm Hi data from the literature, we investigate the role of the cluster environment on the dust content of Virgo spiral galaxies. We show for the first time that the extent of the dust disk is significantly reduced in Hi-deficient galaxies, following remarkably well the observed “truncation” of the Hi disk. The ratio of the submillimetre-to-optical diameter correlates with the Hi-deficiency, suggesting that the cluster environment is able to strip dust as well as gas. These results provide important insights not only into the evolution of cluster galaxies but also into the metal enrichment of the intra-cluster medium

Electric-magnetic duality in linearized Ho\v{r}ava-Lifshitz gravity

Known as a symmetry of vacuum Maxwell equations, the electric-magnetic duality can be lifted actually to a symmetry of an action. The Lagrangian of this action is written in terms of two vector potentials, one electric and one magnetic, and while it is manifestly invariant under duality rotations, it is not manifestly Lorentz covariant. This duality symmetry exists also in linearized gravity in four dimensions, and can be lifted off shell too. In $d$ dimensions, the link between linearized gravity and its dual can also be seen from the point of view of a parental action. This is defined by a first order Lagrangian (with the help of some auxiliary variables) that delivers both Fierz-Pauli theory and its dual. In this work we use this formalism to implement the electric-magnetic duality in the nonrelativistic deviation of Fierz-Pauli theory arising from Ho\v{r}ava-Lifshitz gravity. Because this theory breaks diffeomorphism invariance, one finds that such implementation includes some peculiarities.Comment: v1: 23 pages, 4 figures, edited with LaTeXila 2.4.0 and wxMaxima 12.04.0 for the graphics (Maxima version: 5.27.0). arXiv admin note: text overlap with arXiv:1306.1092 by other authors; v2: 24 pages, 4 figures, references added, negligence (leading to poor version management and miscommunication) rectified; v3: typos and grammar corrected, minor changes to uniformize convention

A FEM-experimental approach for the development of a conceptual linear actuator based on tendril's free coiling

Within the vastness of the plant species, certain living systems show tendril structures whose motion is of particular interest for biomimetic engineers. Tendrils sense and coil around suitable grips, and by shortening in length, they erect the remaining plant body. To achieve contraction, tendrils rotate along their main axis and shift from a linear to a double-spring geometry. This phenomenon is denoted as the free-coiling phase. In this work, with the aim of understanding the fundamentals of the mechanics behind the free coiling, a reverse-engineering approach based on the finite element method was firstly applied. The model consisted of an elongated cylinder with suitable material properties, boundary, and loading conditions, in order to reproduce the kinematics of the tendril. The simulation succeeded in mimicking coiling faithfully and was therefore used to validate a tentative linear actuator model based on the plant’s working principle. More in detail, exploiting shape memory alloy materials to obtain large reversible deformations, the main tendril features were implemented into a nickel-titanium spring-based testing model. The results of the experimental tests confirmed the feasibility of the idea in terms of both functioning principles and actual performance. It can be concluded that the final set-up can be used as a base for a prototype design of a new kind of a linear actuator

Neutral Hydrogen and Star Formation in the Coma-Abell1367 Supercluster

We present preliminary results of a multi-wavelength study focused on the evolution of spiral galaxies in the UV-optical colour-magnitude (CM) diagram. By combining HI, UV and optical observations of the Coma-Abell1367 supercluster we are able to identify galaxies at different stages of their evolution: from healthy star-forming galaxies, to blue HI-poor spirals and transition objects. Our analysis shows that galaxies in the transition region are likely to be the progeny of healthy spirals, whose star-formation has been quenched by the harsh cluster environment. This result suggests that, at least in clusters of galaxies, the migration of galaxies from the blue to the red sequence might be due to environmental processes.Comment: To appear in AIP Conf. Proc., "The Evolution of Galaxies through the Neutral Hydrogen Window", Feb 1-3 2008, Arecibo, eds. R. Minchin & E. Momjian. 4 pages, 2 figure