Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression of ADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, we demonstrate that Pten-deficient prostate tumours are addicted to the NOTCH signalling. Importantly, we find that pharmacological inhibition of γ-secretase promotes growth arrest in both Pten-null and Pten/Trp53-null prostate tumours by triggering cellular senescence. Altogether, our findings describe a novel pro-tumorigenic network that links PTEN loss to ADAM17 and NOTCH signalling, thus providing the rational for the use of γ-secretase inhibitors in advanced prostate cancer patients

Machine learning techniques to estimate the degree of binder activity of reclaimed asphalt pavement

This paper describes the development of novel/state-of-art computational framework to accurately predict the degree of binder activity of a reclaimed asphalt pavement sample as a percentage of the indirect tensile strength (ITS) using a reduced number of input variables that are relatively easy to obtain, namely compaction temperature, air voids and ITS. Different machine learning (ML) techniques were applied to obtain the most accurate data representation model. Specifically, three ML techniques were applied: 6th-degree multivariate polynomial regression with regularization, artificial neural network and random forest regression. The three techniques produced models with very similar precision, reporting a mean absolute error ranging from 12.2 to 12.8% of maximum ITS on the test data set. The work presented in this paper is an evolution in terms of data analysis of the results obtained within the interlaboratory tests conducted by Task Group 5 of the RILEM Technical Committee 264 on Reclaimed Asphalt Pavement. Hence, despite it has strong bonds with this framework, this work was developed independently and can be considered as a natural follow-up

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Advanced characterization of innovative environmentally friendly bituminous mixtures

none1nononeEmiliano PasquiniPasquini, Emilian

I collegamenti ferroviari italiani con i paesi confinanti a est, Austria e Slovenia

I collegamenti infrastrutturali tra l\u2019Italia e l\u2019area geografica coincidente con l\u2019Austria e la Slovenia sono sempre stati molto complessi e difficili poich\ue9 gran parte dei territori austriaco e sloveno \ue8 a carattere montano e di difficile attraversamento. Le prime opere di collegamento furono costruite in epoca romana e congiungevano i principali centri dell\u2019epoca, quali Altinum (Altino), Aquileia, Tergeste (Trieste), Iulia Emona (Lubiana), Celeia (Celje), Santicum (Villach), Virunum (Klagenfurt) e Vindobona (Vienna). Se i Romani furono i primi a costruire nell'area una rete stradale idonea al collegamento delle diverse realt\ue0, l\u2019attuale rete ferroviaria fu costruita per la maggior parte durante l\u2019Impero Austro-Ungarico, e i tracciati delle linee ferroviarie seguirono in gran parte gli stessi percorsi seguiti dai Romani 1800 anni prima. La situazione cambi\uf2 in seguito alla nascita degli stati attualmente esistenti (frammentazione dell\u2019Impero Austro-Ungarico) e con il susseguirsi degli eventi durante il XX secolo (Prima e Seconda Guerra Mondiale, Guerra Fredda), che spostarono pi\uf9 volte i confini degli Stati, modificando l\u2019importanza delle diverse linee ferroviarie e rendendo pi\uf9 difficili i collegamenti tra Italia, Austria e Slovenia. In quest\u2019area geografica, Trieste ha sempre goduto di una posizione strategica, essendo l\u2019unica citt\ue0 con uno sbocco sul mare vicina al centro Europa (Austria, Repubblica Ceca e Ungheria) e le linee ferroviarie furono costruite inizialmente con lo scopo di spostare le merci pi\uf9 velocemente. Se oggi purtroppo le merci seguono anche altri itinerari (quelli per Amburgo o per Rotterdam), con la progettazione e la costruzione dei corridoi europei (rete TEN-T), l\u2019Italia, l\u2019Austria e la Slovenia sono indirizzate a rafforzare i loro collegamenti. Tramite il corridoio Mediterraneo e il corridoio Baltico-Adriatico, Trieste e Venezia saranno collegate con Vienna e Lubiana in maniera maggiormente efficace sia dal punto di vista economico che sociale

Experimental characterization of high-performance fiber-reinforced cold mix asphalt mixtures

Maintenance of existing road pavements assumes increasing interest as the traffic growing produces a faster deterioration of road infrastructures compromising safety and pavement serviceability. In order to guarantee long-lasting pavement repairs, maintenance activities and products must be optimized in terms of both achieved performance and curing times to reach a proper pavement serviceability. This research project focuses on the experimental characterization of a high-performance cold mix asphalt mixture reinforced with three types of fibers (cellulose, glass–cellulose, nylon–polyester–cellulose) dosed at two different contents (0.15% and 0.30% by the aggregate weight). Such materials were investigated at different curing times (1, 7, 14, 28 days) and conditions (dry and wet). Laboratory tests (Marshall, Indirect Tensile, Abrasion and Compactability) usually employed for hot mix asphalts were considered, adjusting the testing procedures taking into account the specific characteristics of cold mixes. Results showed that the mix with 0.15% cellulose fibers provides similar (for curing times of 14 and 28 days) or even higher performance (for curing times within 7 days) than the standard mixture (without fibers). Finally, the last two mixtures were compared with two cold mix asphalt mixes available on the market. The cellulosefiber- reinforced material and the standard one showed enhanced performance, allowing the conclusion that they can be more successfully used in maintenance activities

Performance and Durability of Porous Asphalt Mixtures Manufactured Exclusively with Electric Steel Slags

Electric arc furnace slag (EAFS) and ladle furnace slag (LFS) are by-products of the electric steelmaking sector with suitable properties for use in bituminous mixtures as both coarse and fine aggregates, respectively. In this research, the production of a porous asphalt mixture with an aggregate skeleton consisting exclusively of electric steelmaking slags (using neither natural aggregates nor fillers) is explored. The test program examines the asphalt mixtures in terms of their mechanical performance (abrasion loss and indirect tensile strength), durability (cold abrasion loss, aging, and long-term behavior), water sensitivity, skid and rutting resistance, and permeability. The results of the slag-mixes are compared with a standard mix, manufactured with siliceous aggregates and cement as filler. The porous mixes manufactured with the slags provided similar results to the conventional standard mixtures. Some issues were noted in relation to compaction difficulties and the higher void contents of the slag mixtures, which reduced their resistance to raveling. Other features linked to permeability and skid resistance were largely improved, suggesting that these mixtures are especially suitable for permeable pavements in rainy regions. In conclusion, a porous asphalt mixture was produced with 100% slag aggregates that met current standards for long-lasting and environmentally friendly mixtures.This research was funded by the following entities and grants: the Junta de Castilla y León and FEDER Funds, grant BU119P17 awarded to research group UIC-231; the University of Burgos through grant Y135 GI awarded to the SUCONS group; and, the University of Padua through grant BIRD182754 from the Department of Civil, Environmental and Architectural Engineering (ICEA)