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The refugee's flows have alighted the European political debate boosting nationalistic forces in almost all countries. The aim of this paper is to show that the actual number of asylum seekers does not really allow to talk about a "refugee crises". It argues, however, that the current European Union institutions and procedures are highly insufficient to manage successfully refugee's inflows and asylum requests. A European foreign policy could have helped to prevent refugees' inflows from war-thorn areas such as Afghanistan, Iraq, Eritrea, Libya and Syria. Once the problem is there, the procedures centred on the Dublin Convention are inadequate and the paper provides a few radical suggestions that are made for an EU- centred refugees and asylum seekers management and policy.

La mancanza di solidarietà dimostrata dai governi europei durante le crisi dei rifugiati iniziata nel 2015 ha minato fondamentalmente il progetto di integrazione europea. Il punto di partenza dei governi era certamente contraddittorio: da un lato, l'UE si basa sul principio della libera circolazione delle persone e sui principi di solidarietà tra stati membri e rispetto dei diritti umani. D'altro canto, la politica europea sui rifugiati si basa ancora sull'idea, ribadita nei vari regolamenti di Dublino, secondo cui lo Stato membro che dovrebbe assumersi la responsabilità primaria di ogni richiedente asilo è quello di primo ingresso nell'UE. Inoltre, c'è significativa discrepanza tra i principi su cui si fonda l'UE e le azioni di politica interna ed esterna che essa ha intrapreso. Piuttosto che affrontare questi problemi, riscrivendo i regolamenti e modificando le politiche in atto, i governi dell'UE hanno preferito scaricarsi le responsabilità tra loro, o addirittura verso Paesi terzi. Questo paper affronta tre temi. Il primo concerne i flussi: il numero di arrivi e di richiedenti asilo in asilo giustifica la definizione di crisi dei rifugiati? Il secondo riguarda, invece, la gestione: le regole dell'UE sono adeguate ad affrontare questi numeri? La Convenzione di Dublino emerge sempre più come un tentativo altamente irrealistico di gestire i flussi di rifugiati. Una regolamentazione alternativa potrebbe ridurre le tensioni intra-europee? Il terzo, infine, riguarda la passività con cui l'UE ha visto arrivare rifugiati da zone di guerra: in che misura i Paesi europei hanno effettivamente cercato di evitare crisi internazionali? Il problema dei flussi di rifugiati avrebbe dovuto essere affrontato rafforzando una politica estera comune dell'UE, in grado di contenere i flussi alla fonte, soprattutto dalle aree, come la Siria, l'Afghanistan, l'Iraq e l'Eritrea, che hanno generato un numero importante di rifugiati.

In questo lavoro invece intendiamo identificare, dopo un inquadramento generale della tematica, il grado effettivo o autopercepito di conoscenza della lingua italiana e le principali caratteristiche che l'apprendimento linguistico assume nella popolazione immigrata presente in Italia. Infine, sarà dedicato un focus particolare alla questione dell'apprendimento dell'italiano da parte degli studenti immigrati o di origine immigrata.

Rapporto del Working Package 2 Politiche familiari e demografiche in Europa e in Italia dell'Accordo di collaborazione tra l'Istituto di Ricerche sulla Popolazione e le Politiche Sociali del CNR (CNR-IRPPS) e il Dipartimento per le Politiche della Famiglia (DiPoFam) della Presidenza del Consiglio dei Ministri in materia di Politiche familiari e demografiche: contesto europeo e realtà italiana

Sirtuin 6 (SIRT6) is a member of the sirtuin family NAD+-dependent deacetylases with multiple roles in controlling organism homeostasis, lifespan, and diseases. Due to its complex and opposite functional roles, this sirtuin is considered a two-edged sword in health and disease. Indeed, SIRT6 improves longevity, similarly to the founding yeast member, silent information regulator-2 (Sir2), and modulates genome stability, telomere integrity, transcription, and DNA repair. Its deficiency is associated with chronic inflammation, diabetes, cardiac hypertrophy, obesity, liver dysfunction, muscle/adipocyte disorders, and cancer. Besides, pieces of evidence showed that SIRT6 is a promoter of specific oncogenic pathways, thus disclosing its dual role regarding cancer development. Collectively, these findings suggest that multiple mechanisms, to date not entirely known, underlie the intriguing roles of SIRT6. Here we provide an overview of the current molecular mechanisms through which SIRT6 controls cancer and heart diseases, and describe its recent implications in the atherosclerotic plaque development.

HSV-1, which belongs to the Herpesviridae family, is responsible for different human infections. It is mainly involved in painful, cutaneous infections and in some cases can cause serious disorders such as blindness and encephalitis[1] . Fusion of host membranes with the viral envelope is necessary for the HSV-1 infection mechanism. Penetration is mediated by a group of glycoproteins conserved in all Herpesvirinae subfamilies, such as the glycoproteins B (gB), H (gH), L (gL) and D (gD). The entry process starts with the virus binding to the cell receptor and is followed by fusion between the viral envelope and a cellular membrane mediated by gB and gH/gL via conformational changes[2,3] . The purpose of this work is the evaluation of antiviral activity of several synthetic peptides derived from gH and gL sequences. In detail, we are interested to understand their specific portion involved in membrane interactions and therefore in triggering of the fusion mechanism. Therefore, we have prepared and screened two libraries of overlapping peptides homologous to the ectodomains of the two viral glycoproteins. The peptides were synthesized using the standard solid-phase Fmoc method on a an automatic synthesizer SYRO multisyntec. HPLC-MS was applied for peptides purification. We obtained 80% yields of synthesis and over than 95% of purification. Several assays of viral entry inhibitions have been performed. Between 148 peptides derived from gH, 24 of these have reached 50% of inhibition in a co-treatment assay at 150 µM as final concentration. Interestingly, they are mainly located in the gH ectodomain carboxy-terminal region, suggesting that this portion is essential for the entry mechanism. In the same time none of the gL peptides has shown a clear inhibition effect, supporting its secondary role in the membrane fusion mechanism. Our data support direct involvement of the described domains in membrane fusion, therefore those results are of relevance for the potential development of novel therapeutic compounds to prevent HSV- 1 infections.

BBB plays a critical role in the brain protection against toxic and infectious agents, but also creates an obstacle for effective systemic drug delivery to the CNS. The high impermeability and selectivity preclude the transport of many therapeutic molecules to the CNS, many drugs for neurological disorders do not achieve effective concentration within the brain tissue following intravenous or oral administration. Enhancement of doses or extended administration of drugs, to avoid this problem, often significantly increase systemic toxicity risks. During the last decade, drug delivery into the brain has been extensively investigated and two therapeutic strategies have been developed: invasive and noninvasive techniques.[1] In particular, with the advent of nanomedicine, nanosystems have been proposed as noninvasive methods to cross the BBB and deliver drugs to CNS.[2] Many of these carriers can be transported across in vitro and in vivo BBB models by endocytosis and/or transcytosis.[3] Different CPPs have been used to functionalize nanosystems to increase the cellular uptake. Moreover several studies demonstrated that the peptide gH625 directly translocates across the membrane bilayer and transports into the cytosol several cargoes. Its mechanism of internalization involves the endocytic pathway only partially; it facilitates the escape from endocytic vesicles; and does not show any toxicity. The aim was to evaluate if gH625 can be used to develop efficient nanosystems to deliver therapeutic agents to the brain.

In merito alla gestione degli ingressi e del soggiorno dei cittadini di paesi terzi, il regime migratorio europeo è fondato sulla distinzione tra rifugiati e migranti economici. Questa è una dicotomia tutta politica necessaria a distinguere fra chi ha il diritto al non respingimento alla frontiera, anche quando viene intercettato senza le necessarie autorizzazioni all'ingresso, e chi invece può entrare solo con le necessarie autorizzazioni e a cui, se intercettato alla frontiera, può essere rifiutata l'ammissione e respinto. Questa distinzione individua due differenti procedure per la gestione della ricezione e dell'accoglienza dei flussi migratori in arrivo. Essa trova una sua importante ragione d'essere nel fatto che permette di intercettare due figure sociali di migranti con bisogni sociali differenti e a cui devono essere date risposte politiche e garantiti servizi differenti sia al momento dell'ingresso che nel prosieguo del percorso migratorio.

Here, we examine the influence of surface chemical reactivity toward ambient gases on the performance of nanodevices based on two-dimensional materials “beyond graphene” and novel topological phases of matter. While surface oxidation in ambient conditions was observed for silicene and phosphorene with subsequent reduction of the mobility of charge carriers, nanodevices with active channels of indium selenide, bismuth chalcogenides and transition-metal dichalcogenides are stable in air. However, air-exposed indium selenide suffers of p-type doping due to water decomposition on Se vacancies, whereas the low mobility of charge carriers in transition-metal dichalcogenides increases the response time of nanodevices. Conversely, bismuth chalcogenides require a control of crystalline quality, which could represent a serious hurdle for up scaling. © 2016 Elsevier B.V.

Despite increasing amounts of experimental evidence depicting the involvement of non-coding RNAs in cancer, the study of BRAFV600E-regulated genes has thus far focused mainly on protein-coding ones. Here, we identify and study the microRNAs that BRAFV600E regulates through the ERK pathway. By performing small RNA sequencing on A375 melanoma cells and a vemurafenib- resistant clone that was taken as negative control, we discover miR-204 and miR-211 as the miRNAs most induced by vemurafenib. We also demonstrate that, although belonging to the same family, these two miRNAs have distinctive features. miR-204 is under the control of STAT3 and its expression is induced in amelanotic melanoma cells, where it acts as an e ector of vemurafenib's anti-motility activity by targeting AP1S2. Conversely, miR-211, a known transcriptional target of MITF, is induced in melanotic melanoma cells, where it targets EDEM1 and consequently impairs the degradation of TYROSINASE (TYR) through the ER-associated degradation (ERAD) pathway. In doing so, miR-211 serves as an e ector of vemurafenib's pro-pigmentation activity. We also show that such an increase in pigmentation in turn represents an adaptive response that needs to be overcome using appropriate inhibitors in order to increase the e cacy of vemurafenib. In summary, we unveil the distinct and context-dependent activities exerted by miR-204 family members in melanoma cells. Our work challenges the widely accepted "same miRNA family = same function" rule and provides a rationale for a novel treatment strategy for melanotic melanomas that is based on the combination of ERK pathway inhibitors with pigmentation inhibitors.

Silent information regulator-2 (Sir-2) proteins, or sirtuins, are a highly conserved protein family of histone deacetylases that promote longevity by mediating many of the beneficial effects of calorie restriction which extends life span and reduces the incidence of cancer, cardiovascular disease (CVD), and diabetes. Here, we review the role of sirtuins (SIRT1-7) in vascular homeostasis and diseases by providing an update on the latest knowledge about their roles in endothelial damage and vascular repair mechanisms. Among all sirtuins, in the light of the numerous functions reported on SIRT1 in the vascular system, herein we discuss its roles not only in the control of endothelial cells (EC) functionality but also in other cell types beyond EC, including endothelial progenitor cells (EPC), smooth muscle cells (SMC), and immune cells. Furthermore, we also provide an update on the growing field of compounds under clinical evaluation for the modulation of SIRT1 which, at the state of the art, represents the most promising target for the development of novel drugs against CVD, especially when concomitant with type 2 diabetes

Nanotechnology is an expanding area of study with potentially pivotal applications in a discipline as medicine where new biomedical active molecules or strategies are continuously developing. One of the principal drawbacks for the application of new therapies is the difficulty to cross membranes that represent the main physiological barrier in our body and in all living cells. Membranes are selectively permeable and allow the selective internalization of substances; generally, they form a highly impermeable barrier to most polar and charged molecules, and represent an obstacle for drug delivery, limiting absorption to specific routes and mechanisms. Viruses provide attracting suggestions for the development of targeted drug carriers as they have evolved naturally to deliver their genomes to host cells with high fidelity. A detailed understanding of virus structure and their mechanisms of entry into mammalian cells will facilitate the development and analysis of virus‐based materials for medical applications. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd., Virus‐based nanoparticle for intracellular delivery.

We present the latest results on high-resolution QCL-based THz spectroscopy: the possibility to perform saturated absorption or cavity-enhanced spectroscopy on THz molecular transitions, strengthened by the realization of a new generation THz FCS. © OSA 2015.

High precision THz molecular spectroscopy promises amazing scientific and technological applications, provided that sources with suitable high power, wide tunability and narrow linewidth, such THz Quantum Cascade Lasers [1] are available. In this context, the first application of a QCL phase-locked to a free-standing THz Frequency Comb Synthesizer (FCS) [2] was recently demonstrated, achieving a state of-the-art accuracy of 4×109 in the determination of the absolute frequency of a THz transition [3]. In this experimental report the overall accuracy was limited by the resolution of the Doppler-broadened direct-absorption spectroscopy adopted therein. As a consequence, the the development of high-resolution THz spectroscopic techniques, such as saturatedabsorption spectroscopy (SAS), is a mandatory condition for further accuracy improvements. We therefore report on the evidence of saturation effects in a rotational transition of CH3OH around 2.55 THz, induced by a freerunning continuous-wave QCL [4], confirming the feasibility of QCL-based subDoppler spectroscopy, once provided that the QCL emission linewidth is comparable with, or narrower than the Lamb-dip width. The QCL emission is used for direct-absorption spectroscopy experiments, allowing to study the dependence of the absorption coefficient on gas pressure and laser intensity. A saturation intensity of 25 W/mm2, for a gas pressure of 17 bar, is measured.

Optical resonators are well-established tools commonly used in spectroscopy, they have widespread applications over the whole electromagnetic spectrum, while record-level optical finesses were achieved in the visible/near-IR. In this context, the THz portion of the electromagnetic spectrum is still lacking of such tools. One reason is certainly that, for many years, the THz range has been an underexploited region. However, recent advances in generation and detection of THz radiation, as well as the advent of novel THz-emitting laser sources, such as quantum cascade lasers (QCLs), and the constantly evolving technology of new materials, are now making THz light emerge as a new promising frontier for interdisciplinary research areas. However, among the number of different applications of THz radiation, a central role is played by molecular spectroscopy. In order to further increase the sensitivity of a spectroscopic system, high-finesse cavity resonators represent an attractive tool as they give access to much longer interaction lengths between light and absorbing medium, and could also provide a narrow reference for a QCL, allowing a reduction of its free-running linewidth.We report on two different resonant cavities designs, injected by a continuous-wave quantum cascade laser emitting at 2.55 THz [1]. The two cavities are a V-shaped and a ring shaped resonator, the input/output couplers of both cavities are wire grid polarizers, acting as highly reflective mirrors, and each cavity is equipped with a shifting mirror, in order to tune the cavity length. The achieved ring-cavity finesse is about 63, corresponding to a Q-factor of 2.6×10-5. Due to its geometrical configuration, the V-shaped resonator produces an optical feedback to the QCL, when in resonance. This optical feedback (OF) prevents an accurate finesse measurements, as it broadens the resonance peak profiles. In order to better understand this effect, we injected both the resonators at the same times; the V-shaped cavity is swept across its resonances, while the ring cavity is kept in a position corresponding to the center of a resonance side. In this conditions, any shift of the laser frequency induced by OF will result in a variation of the signal transmitted by the ring cavity. Experimental data have confirmed this effect, that in the future can be exploited for optically locking the QCL frequency to the V-shaped cavity resonance.