Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment

DT Sector Collector electronics design and construction

The CMS detector at LHC is equipped with Drift Tubes (DT) chambers for muon detection and triggering in the barrel region. The Sector Collector (SC) modules collect the track segments reconstructed by on-chamber trigger electronics. Data from different chambers are aligned in time and sent to the subsequent reconstruction processors via optical links. Several FPGA devices performing the processing of the data were designed in VHDL, including spy features to monitor the trigger data flow. A test jig was set up with custom hardware and software in order to fully validate final production boards. Installation and commissioning in CMS provided first experience with the synchronization and monitoring tools

Direct imaging of defect formation in strained organic flexible electronics by Scanning Kelvin Probe Microscopy

The development of new materials and devices for flexible electronics depends crucially on the understanding of how strain affects electronic material properties at the nano-scale. Scanning Kelvin-Probe Microscopy (SKPM) is a unique technique for nanoelectronic investigations as it combines non-invasive measurement of surface topography and surface electrical potential. Here we show that SKPM in non-contact mode is feasible on deformed flexible samples and allows to identify strain induced electronic defects. As an example we apply the technique to investigate the strain response of organic thin film transistors containing TIPS-pentacene patterned on polymer foils. Controlled surface strain is induced in the semiconducting layer by bending the transistor substrate. The amount of local strain is quantified by a mathematical model describing the bending mechanics. We find that the step-wise reduction of device performance at critical bending radii is caused by the formation of nano-cracks in the microcrystal morphology of the TIPS-pentacene film. The cracks are easily identified due to the abrupt variation in SKPM surface potential caused by a local increase in resistance. Importantly, the strong surface adhesion of microcrystals to the elastic dielectric allows to maintain a conductive path also after fracture thus providing the opportunity to attenuate strain effects

Gap ratio in anharmonic charge-density-wave systems

Many experimental systems exist that possess charge-density-wave order in their ground state. While this order should be able to be described with models similar to those used for superconductivity, nearly all systems have a ratio of the charge-density-wave order parameter to the transition temperature that is too high for conventional theories. Recent work explained how this can happen in harmonic systems, but when the lattice distortion gets large, anharmonic effects must play an increasingly important role. Here we study the gap ratio for anharmonic charge-density wave systems to see whether the low-temperature properties possess universality as was seen previously in the transition temperature and to see whether the explanation for the large gap ratios survives for anharmonic systems as well.Comment: (5 pages, 3 figures, ReVTeX

Chiral Fermions on the Lattice through Gauge Fixing -- Perturbation Theory

We study the gauge-fixing approach to the construction of lattice chiral gauge theories in one-loop weak-coupling perturbation theory. We show how infrared properties of the gauge degrees of freedom determine the nature of the continuous phase transition at which we take the continuum limit. The fermion self-energy and the vacuum polarization are calculated, and confirm that, in the abelian case, this approach can be used to put chiral gauge theories on the lattice in four dimensions. We comment on the generalization to the nonabelian case.Comment: 31 pages, 5 figures, two refs. adde

Sviluppo di modelli innovativi per il monitoraggio multiscala degli indicatori di servizi ecosistemici nelle foreste Mediterranee (Progetto MIMOSE).

Gli ecosistemi, attraverso le loro funzioni, forniscono un ampio range di beni e servizi, che risultano fondamentali per il benessere dell’uomo. Questi vengono complessivamente definiti Servizi Ecosistemici (SE). I SE possono essere intesi come un flusso di valori verso la società, quale risultato dello stato e della quantità del capitale naturale disponibile. Il mantenimento degli stocks del capitale naturale può permettere di prevedere i flussi futuri dei SE, assicurando quindi il benessere dell’uomo per le generazioni future. Il progetto FIRB 2012 MIMOSE è finalizzato allo sviluppo di un approccio multiscala innovativo e all’implementazione di strumenti previsionali volti al monitoraggio dei SE in habitat forestali Mediterranei. Un set di indicatori viene considerato per stimare i SE forniti dalle foreste, sviluppando strumenti integrati per il loro monitoraggio multiscala. Le attività di ricerca vertono allo sviluppo di un metodo statistico innovativo per la stima spaziale degli indicatori di SE, sulla base di dati disponibili a diversi livelli di scala spaziale. Sono realizzate mappe wall-to-wall per la fornitura dei SE, derivate da diversi domini spaziali, dal livello di scala locale sino ad aree forestali di grande estensione. I dati sugli indicatori dei SE sono forniti nel contesto di attività di campionamento già stabilite (raccolta dati a livello di aree di saggio e di popolamento), per poi applicare tecniche di spazializzazione per aggregare i dati raccolti su scala locale a livelli di scala più ampia (paesaggio, scala regionale); l’approccio utilizzato viene valutato attraverso l’applicazione di strumenti di monitoraggio in un set di aree test. Si procede quindi alla valutazione dei cambiamenti spazio-temporali nella previsione dei SE, considerando indicatori sensibili alla gestione forestale, ovvero capaci di evidenziare cambiamenti nella previsione di fornitura di beni e servizi ad opera dei sistemi forestali, in relazione a differenti scenari gestionali, con l’obiettivo di fornire indicazioni ai gestori forestali ed alle comunità locali per l’applicazione di pratiche di gestione che possano mantenere o incrementare la fornitura dei SE in un preciso contesto territoriale. Questo progetto permette di realizzare un’attenta analisi dei gaps esistenti negli attuali schemi di inventariazione in relazione alla fornitura dei SE, con l’obiettivo di dare indicazioni utili all’implementazione ed integrazione degli stessi mediante individuazione di nuovi indicatori, nell’ottica di una gestione forestale sostenibile. Le attività di ricerca in corso possono concretamente contribuire all’incorporazione dei SE nei processi decisionali connessi alla gestione dei paesaggi forestali, fornendo un’opportunità per comprendere la congruenza tra i diversi SE negli ambienti forestali

Instanton Calculus and Nonperturbative Relations in N=2 Supersymmetric Gauge Theories

Using instanton calculus we check, in the weak coupling region, the nonperturbative relation =i\pi\left(\cf-{a\over 2} {\partial\cf\over\partial a}\right) obtained for a N=2 globally supersymmetric gauge theory. Our computations are performed for instantons of winding number k, up to k=2 and turn out to agree with previous nonperturbative results.Comment: 18 pages, latex file, no figure