263 research outputs found

    Per una ricapitalizzazione efficacenete co-creativa dei sistemi territoriali italiani

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    La trasformazione creativa (innovazione) non dovrebbe essere immaginata se non come emergente dall’interazione interna (immanente) ai soggetti individuali o inter-individuali, piuttosto che da istanze separate e superiori (trascendenti). Il compito del planning dovrebbe quindi essere quello di rendere percepibili le potenzialità di cambiamento emergenti dall’interazione della molteplicità di detentori di quote di capitale urbano (stakeholder), che includono in pratica la totalità dei soggetti, e di fornire loro validi framework di orientamento e di scambio tra differenti, e spesso inconciliabili, sistemi di ‘valori’. Sono insomma richiesti approcci innovativi all’‘urbano’, per lo più contrastanti con le tradizionali prassi di investimento infrastrutturale, realizzate a scapito dell’investimento in ‘capitale umano’. Per superare la vieta dicotomia tra approcci top-down e bottom-up appare inoltro opportuno far riferimento a un nuovo modello di governance caratterizzato da reti auto-organizzate assimilabili a un fenomeno spontaneo guidato da processi sociali più che da obiettivi politici. A questo modello social di governance fanno riferimento i cosiddetti Living Lab urbani e territoriali, da considerare come veri e propri ecosistemi di agenzie che, interagendo co-creativamente, sembrano poter costituire un utile riferimento per l’integrazione multi scalare dei livelli di governo e che, attraverso la condivisione di un’idea di impresa e/o di una problematica, sembrano anche in grado di produrre concreti effetti di rigenerazione urbano-territoriale

    Aminoacid substitutions in the glycine zipper affect the conformational stability of amyloid beta fibrils

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    The aggregation of amyloid-beta peptides is associated with the pathogenesis of Alzheimer’s disease. The hydrophobic core of the amyloid beta sequence contains a GxxxG repeated motif, called glycine zipper, which involves crucial residues for assuring stability and promoting the process of fibril formation. Mutations in this motif lead to a completely different oligomerization pathway and rate of fibril formation. In this work, we have tested G33L and G37L residue substitutions by molecular dynamics simulations. We found that both protein mutations may lead to remarkable changes in the fibril conformational stability. Results suggest the disruption of the glycine zipper as a possible strategy to reduce the aggregation propensity of amyloid beta peptides. On the basis of our data, further investigations may consider this key region as a binding site to design/discover novel effective inhibitors. Communicated by Ramaswamy H. Sarma

    Study of Fe/Silicalite catalyst for the N2O oxidation of benzene to phenol

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    A set of Fe-silicalite samples of MFI structure have been prepared by the hydrothermal technique, followed by steaming and by further chemical treating of the solid. After characterisation by nitrogen adsorption/desorption, X-ray diffraction (XRD), scanning electron microscopy-electron probe micro analysis (SEM-EPMA), the samples have been tested as catalysts for the oxidation of benzene to phenol by N2O. The best performing catalyst has been studied also by temperature programmed desorption-mass spectrometry and temperature programmed reaction-mass spectrometry (TPD-TPR-MS), after pre-adsorption of both reactants and products. It was found that phenol forms when N2O is adsorbed first, followed by benzene. Almost no phenol formation was observed when adsorbing benzene before N2O. Furthermore, on this catalyst N2O decomposed since 50\ub0C or less, forming gaseous N2 and adsorbed oxygen, which started to become available for the oxidation of benzene since 100\u2013200\ub0C. However, the so formed phenol remained adsorbed onto the catalyst. It desorbed within the 225\u2013425\ub0C temperature range, with a maximum around 300\ub0C

    Perovskite catalysts for the catalytic flameless combustion of methane : preparation by flame-hydrolysis and characterisation by TPD-TPR-MS and EPR

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    A new method was employed for the preparation of a set of lanthanum cobaltites of general formula La1-(x)M(x)CoO3+(\u3b4) with M=Ce, Eu and x=0, 0.05, 0.1, 0.2. All the samples thus prepared were nanostructured, thermally very stable and characterised by highly crystalline perovskite-like structure and high surface area. Their activity as catalysts for the catalytic tameless combustion (CFC) of methane was by ca. one order of magnitude higher than that of their analogues, prepared through the usual calcination-milling (CM) procedure. Adsorption of oxygen was accompanied by formation of paramagnetic species. Desorption of preadsorbed oxygen was dependent on the nature of the doping element and on the value of the stoichiometric coefficient x of their formula. A correlation between the temperature of the maximal rate of oxygen release and catalytic activity was found. The following scale of activity for the title reaction versus x values could be set up: 0.1Ce>0.05Ce>0>0.05Eu>0.1 Eu 430.2Ce. The higher activity of Ce-doped catalysts as compared to those doped with Eu was found to be related to the strength of the bond between oxygen and Co ions

    A novel mitochondrial Kv1.3-caveolin axis controls cell survival and apoptosis

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    The voltage-gated potassium channel Kv1.3 plays an apparent dual physiological role by participating in activation and proliferation of leukocytes as well as promoting apoptosis in several types of tumor cells. Therefore, Kv1.3 is considered a potential pharmacological target for immunodeficiency and cancer. Different cellular locations of Kv1.3, at the plasma membrane or the mitochondria, could be responsible for such duality. While plasma membrane Kv1.3 facilitates proliferation, the mitochondrial channel modulates apoptotic signaling. Several molecular determinants of Kv1.3 drive the channel to the cell surface, but no information is available about its mitochondrial targeting. Caveolins, which are able to modulate cell survival, participate in the plasma membrane targeting of Kv1.3. The channel, via a caveolin-binding domain (CDB), associates with caveolin 1 (Cav1), which localizes Kv1.3 to lipid raft membrane microdomains. The aim of our study was to understand the role of such interactions not only for channel targeting but also for cell survival in mammalian cells. By using a caveolin association-deficient channel (Kv1.3 CDBless), we demonstrate here that while the Kv1.3-Cav1 interaction is responsible for the channel localization in the plasma membrane, a lack of such interaction accumulates Kv1.3 in the mitochondria. Kv1.3 CDBless severely affects mitochondrial physiology and cell survival, indicating that a functional link of Kv1.3 with Cav1 within the mitochondria modulates the pro-apoptotic effects of the channel. Therefore, the balance exerted by these two complementary mechanisms fine-tune the physiological role of Kv1.3 during cell survival or apoptosis. Our data highlight an unexpected role for the mitochondrial caveolin-Kv1.3 axis during cell survival and apoptosis

    Estratigrafía de alta resolución de depósitos de flujos gravitacionales de la Formación Los Molles (Grupo Cuyo - Jurásico) en la región de La Jardinera, cuenca Neuquina

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    El Grupo Cuyo en el área del arroyo La Jardinera (Pliensbachiano a Caloviano Temprano) refleja una fisiografía de cuenca de plataforma y talud. Una discordancia de orden mayor define la culminación de una espesa sucesión de turbiditas y representa un límite de secuencia de 2do orden. La más antigua secuencia de 2do orden comprende el tramo basal de la Formación Los Molles e incluye un ciclo transgresivo-regresivo asignado a estratos de base de talud y fondo de cuenca. La secuencia más joven, que incluye el resto del Grupo Cuyo, consiste de una sucesión regresiva puntuada por varios desplazamientos abruptos de elementos fisiográficos (límites de secuencia de 3er orden). Las secuencias depositacionales de 3er orden incluyen depósitos de talud y de base de talud del Aaleniano de la Formación Los Molles, facies de plataforma del Bajociano Temprano en la transición entre las formaciones Los Molles y Lajas, y sedimentitas de plataforma interna a nearshore del Bajociano medio a tardío de la Formación Lajas, que es a su vez cubierta por depósitos del Bathoniano aluvial de la Formación Challacó. Ciclos de más alta frecuencia alternan en la sucesión y han controlado el origen, depositación y abandono de los elementos arquitecturales. Análisis de facies y de elementos arquitecturales indican que los depósitos gravitatorios densos de la Formación Los Molles encuadran en un modelo de rampa submarina. Los tres tipos de flujos gravitacionales (GF) han sido relacionados a caídas del nivel del mar de 4to orden. Los GF1 fueron asignados a flujos hiperpícnicos producidos durante un cortejo temprano de mar bajo de 4to orden, coevo con incisión fluvial en la plataforma, que evolucionaran a flujos turbidíticos en el talud, produciendo cargas de pulsos depositacionales cuya signatura composicional es fluvial. El sistema de GF1 incluye canales relativamente pequeños sobre el talud, lóbulos bien desarrollados en la base del talud y la planicie de fondo de cuenca proximales, así como lóbulos adventicios en la planicie del fondo de cuenca. Los estratos GF2 fueron asignados a flujos hiperpícnicos influenciados por un componente oscilatorio y relacionados a cortejos tardíos de mar bajo de 4to orden, que también incluyen relleno de canales incididos. Ellos están caracterizados en el talud por areniscas onduladas y laminadas ampliamente distribuidas y facies heterolíticas, que incluyen scours de bajo relieve en sus porciones centrales. Ellos representan flujos densos más diluidos y de grano más fino con respecto a los GF1. Los GF3, también asociados con cuñas de mar bajo de 4to orden, comprenden depósitos de flujos en masa y debris de talud y de base de talud, que representan clásicos surges de corta duración causados por debilidades en taludes relativamente abruptos. Los cortejos transgresivos y de mar alto de 4to orden llevaron al abandono de la etapa turbidítica y extensiva depositación de fango.The Pliensbachian to Early Callovian Cuyo Group in the Arroyo La Jardinera area reflects a shelf-slope-basin plain physiography. A major unconformity defines the onset of a thick turbidite succession and represents a 2nd order sequence boundary. The older 2nd order depositional sequence comprises the base of Los Molles Formation and includes a transgressive-regressive cycle ascribed to basin plain and slope rise strata. The younger one, which includes the rest of the Cuyo Group, consists of a regressive succession punctuated by several abrupt shifts of physiographic elements (3rd order sequence boundaries). The 3rd order depositional sequences include Aalenian slope rise and slope deposits in the Los Molles Formation, Early Bajocian shelfal facies at the transition of the Los Molles and Lajas formations, and Middle to Late Bajocian inner shelf to nearshore strata in the Lajas Formation that are overlain by Bathonian alluvial deposits of the Challacó Formation. Higher frequency cycles punctuate the succession and have controlled the origin, deposition and abandonment of the architectural elements. Facies and architectural elements analyses indicate that gravity flow deposits in the Los Molles Formation fit in a submarine ramp model. The three identified gravity flow (GF) types have been related to 4th order relative sea-level falls. The GF1 was ascribed to hyperpycnal flows produced during 4th order early lowstand, coeval to fluvial incision on the shelf, which were ignited in the slope and produced depletive depositional pulses with a fluvial compositional signature. The GF1 system includes relatively small channels in the slope, well-developed lobes in the slope rise and proximal basin plain, and lobe fringes in the basin plain. The GF2 strata were ascribed to hyperpycnal flows influenced by an oscillatory component and related to the 4th order late lowstand systems tract that also includes the incised channels fill. They are characterized in the slope by widespread, undulating and laminated sandstone and heterolithic facies, which include low relief scours at their central portions. They represent more diluted and finer-grained density flows relative to the GF1. The GF3, also associated with the 4th order lowstand wedge, comprises mass and debris flow deposits in the slope and slope rise that represent classical, short-lived surges caused by slope failures on relatively steep slopes. The 4th order transgressive and highstand systems tracts led to the abandonment of the turbidite stages and widespread mud deposition.Fil: Paim, Paulo S. G.. Universidad de Vale do Rio dos Sinos; BrasilFil: Silveira, Ariane. Universidad de Vale do Rio dos Sinos; BrasilFil: Lavina, Ernesto L. C.. Universidad de Vale do Rio dos Sinos; BrasilFil: Faccini, Ubiratan F.. Universidad de Vale do Rio dos Sinos; BrasilFil: Leanza, Hector Armando. Secretaría de Industria y Minería. Servicio Geológico Minero Argentino; Argentina. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Teixeira de Oliveira, J. M. M.. Universidad de Vale do Rio dos Sinos; BrasilFil: D'Avila, Roberto S. F.. Universidad de Vale do Rio dos Sinos; Brasil. Petrobras Argentina S.a; Argentin

    Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

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    BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation

    Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

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    Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondria! energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/beta-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondria! ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondria! energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologie

    Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

    Get PDF
    Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondria! energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/beta-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondria! ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondria! energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologie

    Design of the ELIMAIA ion collection system

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    A system of permanent magnet quadrupoles (PMQs) is going to be realized byINFNLNS to be used as a collection system for the injection of laser driven ionbeams up to 60 AMeV in an energy selector based on four resistive dipoles. Thissystem is the first element of the ELIMED (ELI-Beamlines MEDical andMultidisciplinary applications) beam transport, dosimetry and irradiation linethat will be developed by INFN-LNS (It) and installed at the ELI-Beamlinesfacility in Prague (Cz). ELIMED will be the first users open transportbeam-line where a controlled laser-driven ion beam will be used formultidisciplinary researches. The definition of well specified characteristics,both in terms of performances and field quality, of the magnetic lenses iscrucial for the system realization, for the accurate study of the beam dynamicsand for the proper matching with the magnetic selection system which will bedesigned in the next months. Here, we report the design of the collection system and the adopted solutionsin order to realize a robust system form the magnetic point of view. Moreover,the first preliminary transport simulations are also described
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