Support for network-based user mobility with LISP

Projecte realitzat en el marc d'un programa de mobilitat amb el Politecnico di TorinoThe goal of this work is developing the most possibly abstract solution for making a user roam in different networks, without dropping his active connections. Better, design a network architecture in charge of maintaining user's connections and being transparent to the user at the same time

Analisi della popolazione dei detriti in ambiente geostazionario

Si tratta del problema dei detriti spaziali in ambiente geostazionario, in particolare del loro impatto ambientale, volto all'identificazione dei più pericolosi rispetto ai satelliti operativi presenti. Si propone una metodologia di identificazione per i corpi a più elevato rischi ambientale, in vista di possibili manovre di rimozioneope

Pensar la seguridad desde el miedo

Tras el crimen del chofer de la línea 620 asistimos a una serie de escenas policiales performáticas y televisadas: Berni atacado por colectiveros en una manifestación fuera de su jurisdicción, operativos nocturnos para detener a colectiveros y retenes en los que revisaban a todos los pasajeros que viajaban por Ruta 3. Respuestas torpes, improvisadas y representaciones escenográficas que, en un escenario caldeado por la crisis, ya dejaron de ejercer su magia. ¿Por qué el progresismo insiste en regalarle la agenda de seguridad a la derecha?Fil: Frederic, Sabina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencias Sociales; ArgentinaFil: Galvani, Mariana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentin

Artificial co-drivers as a universal enabling technology for future intelligent vehicles and transportation systems

This position paper introduces the concept of artificial “co-drivers” as an enabling technology for future intelligent transportation systems. In Sections I and II, the design principles of co-drivers are introduced and framed within general human–robot interactions. Several contributing theories and technologies are reviewed, specifically those relating to relevant cognitive architectures, human-like sensory-motor strategies, and the emulation theory of cognition. In Sections III and IV, we present the co-driver developed for the EU project interactIVe as an example instantiation of this notion, demonstrating how it conforms to the given guidelines. We also present substantive experimental results and clarify the limitations and performance of the current implementation. In Sections IV and V, we analyze the impact of the co-driver technology. In particular, we identify a range of application fields, showing how it constitutes a universal enabling technology for both smart vehicles and cooperative systems, and naturally sets out a program for future research

Treatment with a GSK-3β/HDAC Dual Inhibitor Restores Neuronal Survival and Maturation in an In Vitro and In Vivo Model of CDKL5 Deficiency Disorder

open11noFunding: This research was funded by the Telethon foundation (grant number GGP19045, awarded to E.C.), and by the Italian parent association “CDKL5 insieme verso la cura” (to E.C.).Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a rare neurodevelopmental disorder characterized by early-onset seizures and severe cognitive, motor, and visual impairments. To date there are no therapies for CDKL5 deficiency disorder (CDD). In view of the severity of the neurological phenotype of CDD patients it is widely assumed that CDKL5 may influence the activity of a variety of cellular pathways, suggesting that an approach aimed at targeting multiple cellular pathways simultaneously might be more effective for CDD. Previous findings showed that a single-target therapy aimed at normalizing impaired GSK-3β or histone deacetylase (HDAC) activity improved neurodevelopmental and cognitive alterations in a mouse model of CDD. Here we tested the ability of a first-in-class GSK-3β/HDAC dual inhibitor, Compound 11 (C11), to rescue CDD-related phenotypes. We found that C11, through inhibition of GSK-3β and HDAC6 activity, not only restored maturation, but also significantly improved survival of both human CDKL5-deficient cells and hippocampal neurons from Cdkl5 KO mice. Importantly, in vivo treatment with C11 restored synapse development, neuronal survival, and microglia over-activation, and improved motor and cognitive abilities of Cdkl5 KO mice, suggesting that dual GSK-3β/HDAC6 inhibitor therapy may have a wider therapeutic benefit in CDD patients.openLoi, Manuela; Gennaccaro, Laura; Fuchs, Claudia; Trazzi, Stefania; Medici, Giorgio; Galvani, Giuseppe; Mottolese, Nicola; Tassinari, Marianna; Giorgini, Roberto Rimondini; Milelli, Andrea; Ciani, ElisabettaLoi, Manuela; Gennaccaro, Laura; Fuchs, Claudia; Trazzi, Stefania; Medici, Giorgio; Galvani, Giuseppe; Mottolese, Nicola; Tassinari, Marianna; Giorgini, Roberto Rimondini; Milelli, Andrea; Ciani, Elisabett

Are FGFR and IDH1-2 alterations a positive prognostic factor in intrahepatic cholangiocarcinoma? An unresolved issue

Despite representing some of the most common and investigated molecular changes in intrahepatic cholangiocarcinoma (iCCA), the prognostic role of FGFR and IDH1/2 alterations still remains an open question. In this review we provide a critical analysis of available literature data regarding this topic, underlining the strengths and pitfalls of each study reported. Despite the overall poor quality of current available studies, a general trend toward a better overall survival for FGFR2 rearrangements and, possibly, for FGFR2-3 alterations can be inferred. On the other hand, the positive prognostic role of IDH1/2 mutation seems much more uncertain. In this scenario, better designed clinical trials in these subsets of iCCA patients are needed in order to get definitive conclusions on this issue

INCLUSÃO DA PESSOA COM DEFICIÊNCIA FÍSICA NO MERCADO DE TRABALHO: SATISFAÇÃO OU DESPRAZER?

O objetivo desta pesquisa foi analisar o grau de satisfação de pessoas com deficiência física incluídas no mercado de trabalho da União dos Deficientes Físicos - UDEFA de Araraquara, localizada no interior de São Paulo, que tem como principal responsabilidade incluir as pessoas com deficiência físca no mercado de trabalho oferecendo cursos preparatórios e em seguida o encaminhamento para empresas parceiras. Essa amostra contou com a colaboração de alguns dos deficientes físicos incluídos no mercado de trabalho via UDEFA, totalizando 15 sujeitos. Para alcançar os objetivos propostos, os participantes responderam um questionário seguindo a Escala Likert. Os resultaos revelaram que as pessoas com deficiência física incluídos no mercado de trabalho por intermédio da UDEFA encontram-se satisfeitas com trabalho atual, com seus salários, com as relações estabelecidas com seus companheiros, superiores e estão abertos a novas propostas. Concluímos que as pessoas com deficiência física também estão de modo geral satisfeitas com a adequação e a acessibilidade em seus locais de trabalho, o que de fato, é de suma importância para esse público alvo.   &nbsp

Metabolism of the EGFR tyrosin kinase inhibitor gefitinib by cytochrome P450 1A1 enzyme in EGFR-wild type non small cell lung cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Gefitinib is a tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) especially effective in tumors with activating EGFR gene mutations while EGFR wild-type non small cell lung cancer (NSCLC) patients at present do not benefit from this treatment.</p> <p>The primary site of gefitinib metabolism is the liver, nevertheless tumor cell metabolism can significantly affect treatment effectiveness.</p> <p>Results</p> <p>In this study, we investigated the intracellular metabolism of gefitinib in a panel of EGFR wild-type gefitinib-sensitive and -resistant NSCLC cell lines, assessing the role of cytochrome P450 1A1 (CYP1A1) inhibition on gefitinib efficacy. Our results indicate that there is a significant difference in drug metabolism between gefitinib-sensitive and -resistant cell lines. Unexpectedly, only sensitive cells metabolized gefitinib, producing metabolites which were detected both inside and outside the cells. As a consequence of gefitinib metabolism, the intracellular level of gefitinib was markedly reduced after 12-24 h of treatment. Consistent with this observation, RT-PCR analysis and EROD assay showed that mRNA and activity of CYP1A1 were present at significant levels and were induced by gefitinib only in sensitive cells. Gefitinib metabolism was elevated in crowded cells, stimulated by exposure to cigarette smoke extract and prevented by hypoxic condition. It is worth noting that the metabolism of gefitinib in the sensitive cells is a consequence and not the cause of drug responsiveness, indeed treatment with a CYP1A1 inhibitor increased the efficacy of the drug because it prevented the fall in intracellular gefitinib level and significantly enhanced the inhibition of EGFR autophosphorylation, MAPK and PI3K/AKT/mTOR signalling pathways and cell proliferation.</p> <p>Conclusion</p> <p>Our findings suggest that gefitinib metabolism in lung cancer cells, elicited by CYP1A1 activity, might represent an early assessment of gefitinib responsiveness in NSCLC cells lacking activating mutations. On the other hand, in metabolizing cells, the inhibition of CYP1A1 might lead to increased local exposure to the active drug and thus increase gefitinib potency.</p

Salivary and serum irisin in healthy adults before and after exercise

Irisin is an exercise-induced cytokine mainly secreted by myocytes. Circulating level of irisin can increase in response to acute exercise, promoting pleiotropic effects on health. Generally, irisin is evaluated in blood, however, its collection is invasive. Saliva sample would not have any risk associated with blood collection and would represent a less invasive method for irisin detection. Until now, there are only a few studies that have analyzed irisin levels in saliva. In the present research, five healthy male adults performed an incremental exercise until exhaustion on cycle ergometer. Serum and saliva samples were collected before exercise and 15min, 24h and 48h after reaching the exhaustion. Irisin was detected by ELISA assay. Serum and salivary irisin levels increased from baseline to 24h post exercise and reverted to basal levels after 48h of rest. A significant rise of both serum and salivary irisin level at 24h (p≤0.05) compared to baseline levels was found. Furthermore, a significant correlation between irisin percentage change in serum and saliva from baseline to 24h post exercise was detected (r=0.92, p<0.05). Despite the relatively limited sample, this research suggests that collecting saliva samples might represent a valid and less invasive method to detect irisin level changes induced by exercise