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Flexible optical networks require reconfigurable devices with operation on a wavelength range of several tens of nanometers, hitless tuneability (i.e. transparency to other channels during reconfiguration), and polarization independence. All these requirements have not been achieved yet in a single photonic integrated device and this is the reason why the potential of integrated photonics is still largely unexploited in the nodes of optical communication networks. Here we report on a fully-reconfigurable add-drop silicon photonic filter, which can be tuned well beyond the extended C-band (almost 100 nm) in a complete hitless (>35 dB channel isolation) and polarization transparent (1.2 dB polarization dependent loss) way. This achievement is the result of blended strategies applied to the design, calibration, tuning and control of the device. Transmission quality assessment on dual polarization 100 Gbit/s (QPSK) and 200 Gbit/s (16-QAM) signals demonstrates the suitability for dynamic bandwidth allocation in core networks, backhaul networks, intra- and inter-datacenter interconnects. Reconfigurable wavelength-selective devices are essential components of flexible optical networks. Here the authors show a silicon-photonic add-drop multiplexer meeting the strict requirements of telecom systems in terms of broadband operation range, hitless tunability and polarization transparency.

Previous studies demonstrated the possibility of targeting tumor-angiogenic endothelial cells with positively charged nanocarriers, such as cationic liposomes. We investigated the active targeting potential of positively charged nanoparticles in combination with the heat-induced drug release function of thermosensitive liposomes (TSL). This novel dual-targeted approach via cationic TSL (CTSL) was thoroughly explored using either a novel synthetic phospholipid 1,2-dipalmitoyl- -glycero-3-phosphodiglycerol (DPPG ) or a conventional polyethylene glycol (PEG) surface modification. Anionic particles containing either DPPG or PEG were also included in the study to highlight difference in tumor enrichment driven by surface charge. With this study, we aim to provide a deep insight into the main differences between DPPG - and PEG-functionalized liposomes, focusing on the delivery of a well-known cytotoxic drug (doxorubicin; DOX) in combination with local hyperthermia (HT, 41-43°C). DPPG - and PEG-based cationic TSLs (PG -CTSL/PEG-CTSL) were thoroughly analyzed for size, surface charge, and heat-triggered DOX release. Cancer cell targeting and DOX delivery was evaluated by FACS, fluorescence imaging, and HPLC. In vivo particle behavior was analyzed by assessing DOX biodistribution with local HT application in tumor-bearing animals. The absence of PEG in PG -CTSL promoted more efficient liposome-cell interactions, resulting in a higher DOX delivery and cancer cell toxicity compared with PEG-CTSL. By exploiting the dual-targeting function of CTSLs, we were able to selectively trigger DOX release in the intracellular compartment by HT. When tested in vivo, local HT promoted an increase in intratumoral DOX levels for all (C)TSLs tested, with DOX enrichment factors ranging from 3 to 14-fold depending on the type of formulation. Cationic particles showed lower hemocompatibility than their anionic counterparts, which was partially mitigated when PEG was grafted on the liposome surface. DPPG -based anionic TSL showed optimal local drug delivery compared to all other formulations tested, demonstrating the potential advantages of using DPPG lipid in designing liposomes for tumor-targeted applications.

The outbreak of the Yom Kippur War and the oil crisis that followed were among the main challenges facing Italian diplomacy during the 1970s. Economic concerns related to energy dependence, historical relations with the Arab world, and domestic policy priorities all led the country to adopt a point of view that partly clashed with that of its allies, including the United States. The article outlines the Italian attitude to the crisis, from the activities in the European Community framework to the unilateral initiatives toward the Arab countries, by an analysis of documents from the private archives of Aldo Moro, the Italian Foreign Minister and Italy’s key foreign-policy player during that period.

: The tumor homing characteristics of mesenchymal stem cells (MSCs) make them attractive vehicles for the tumor-specific delivery of therapeutic agents, such as the sodium iodide symporter (NIS). NIS is a theranostic protein that allows non-invasive monitoring of the biodistribution of functional NIS expression by radioiodine imaging as well as the therapeutic application of I. To gain local and temporal control of transgene expression, and thereby improve tumor selectivity, we engineered MSCs to express the gene under control of a heat-inducible HSP70B promoter (HSP70B-NIS-MSCs). : NIS induction in heat-treated HSP70B-NIS-MSCs was verified by I uptake assay, RT-PCR, Western blot and immunofluorescence staining. HSP70B-NIS-MSCs were then injected i.v. into mice carrying subcutaneous hepatocellular carcinoma HuH7 xenografts, and hyperthermia (1 h at 41°C) was locally applied to the tumor. 0 - 72 h later radioiodine uptake was assessed by I-scintigraphy. The most effective uptake regime was then selected for I therapy. : The HSP70B promoter showed low basal activity and was significantly induced in response to heat. , the highest tumoral iodine accumulation was seen 12 h after application of hyperthermia. HSP70B-NIS-MSC-mediated I therapy combined with hyperthermia resulted in a significantly reduced tumor growth with prolonged survival as compared to control groups. : The heat-inducible HSP70B promoter allows hyperthermia-induced spatial and temporal control of MSC-mediated theranostic gene radiotherapy with efficient tumor-selective and temperature-dependent accumulation of radioiodine in heat-treated tumors.

The tumor homing characteristics of mesenchymal stem cells (MSCs) make them attractive vehicles for the tumor-specific delivery of therapeutic agents, such as the sodium iodide symporter (NIS). NIS is a theranostic protein that allows non-invasive monitoring of the in vivo biodistribution of functional NIS expression by radioiodine imaging as well as the therapeutic application of 131I. To enhance the actively recruitment of MSCs to growing tumor stroma and thereby trigger targeted delivery of the NIS gene to the tumor, we examined the combination with regional hyperthermia, as heat induces the secretion of immunomodulatory chemokines, cytokines and growth factors, well-known attractants of MSCs. Human hepatocellular carcinoma cells (HuH7) were heat-treated in a water bath at 41 °C for 1h, followed by incubation at 37 °C for 0-48h. mRNA and protein levels of chemokines involved in MSC migration was analyzed by RT-PCR and ELISA. Chemotaxis of MSCs in relation to a gradient of supernatants was tested in a 3D live cell tracking migration assay. In a subcutaneous HuH7 mouse xenograft tumor model, a single systemic injection of CMV-NIS-MSCs was applied 6h, 24h, 48h after or 24h, 48h before hyperthermia treatment and tumoral 123I accumulation was assessed by 123I-scintigraphy. Ex vivo NIS analysis of tumor sections was performed by RT-PCR and immunohistochemistry. The optimal imaging regime was then used for a 131I therapy study. Chemokine mRNA and protein analysis indicated a substantial increase in expression levels of chemokines and growth factors, involved in MSC tumor homing, after heat exposure. In addition, MSCs showed directed migration towards the supernatant of thermo-stimulated cancer cells. In vivo, with the optimal regime, we observed a significantly increased uptake of 123I in tumors of heat-treated animals (41 °C) when thermostimulated 24h after CMV-NIS-MSC injection compared to control animals (37 °C). Immunohistochemical staining of tumor sections showed strong tumoral NIS-specific immunoreactivity and RT-PCR an increased NIS mRNA expression in heat-treated tumors, thereby confirming tumor-selective, temperature-dependent MSC migration. CMV-NIS-MSC-mediated 131I therapy combined with regional hyperthermia resulted in a reduced tumor growth that was associated with prolonged survival of regional heat-treated animals compared to normothermic mice and to the saline control group. In summary, we have demonstrated a significantly increased, selective MSC migration towards the tumor stroma after regional hyperthermia in the 123I imaging study. The combination of MSC-mediated NIS gene therapy with mild regional hyperthermia resulting in stimulated therapeutic efficacy of NIS-mediated 131I therapy.

L'éclatement de la guerre du Yom Kippour en octobre 1973 et la crise pétrolière suivante constituent des enjeux majeurs pour la diplomatie italienne des années 1970. Des craintes économiques liées à la dépendance énergétique, des rapports historiques avec le monde arabe et des considérations de politique interne poussent en effet le pays à adopter un point de vue partiellement en contraste avec ses alliés, et notamment avec les États-Unis. L'article a pour objectif de décrire l'attitude italienne face à la crise, de l'engagement communautaire aux initiatives unilatérales vers les pays arabes, en s'appuyant sur les documents des archives privées du ministre des Affaires étrangères Aldo Moro, un des acteurs-clés de la politique étrangère italienne pendant cette période. The outbreak of the Yom Kippur War and the oil crisis that followed were among the main challenges facing Italian diplomacy during the 1970s. Economic concerns related to energy dependence, historical relations with the Arab world, and domestic policy priorities all led the country to adopt a point of view that partly clashed with that of its allies, including the United States. The article outlines the Italian attitude to the crisis, from the activities in the European Community framework to the unilateral initiatives toward the Arab countries, by an analysis of documents from the private archives of Aldo Moro, the Italian Foreign Minister and Italy's key foreign-policy player during that period.

RésuméL’éclatement de la guerre du Yom Kippour en octobre 1973 et la crise pétrolière suivante constituent des enjeux majeurs pour la diplomatie italienne des années 1970. Des craintes économiques liées à la dépendance énergétique, des rapports historiques avec le monde arabe et des considérations de politique interne poussent en effet le pays à adopter un point de vue partiellement en contraste avec ses alliés, et notamment avec les États-Unis. L’article a pour objectif de décrire l’attitude italienne face à la crise, de l’engagement communautaire aux initiatives unilatérales vers les pays arabes, en s’appuyant sur les documents des archives privées du ministre des Affaires étrangères Aldo Moro, un des acteurs-clés de la politique étrangère italienne pendant cette période. SummaryThe outbreak of the Yom Kippur War and the oil crisis that followed were among the main challenges facing Italian diplomacy during the 1970s. Economic concerns related to energy dependence, historical relations with the Arab world, and domestic policy priorities all led the country to adopt a point of view that partly clashed with that of its allies, including the United States. The article outlines the Italian attitude to the crisis, from the activities in the European Community framework to the unilateral initiatives toward the Arab countries, by an analysis of documents from the private archives of Aldo Moro, the Italian Foreign Minister and Italy’s key foreign-policy player during that period.

Fermi level pinning in doped metal oxide (MO) nanocrystals (NCs) results in the formation of depletion layers, which affect their optical and electronic properties, and ultimately their application in smart optoelectronics, photocatalysis, or energy storage. For a precise control over functionality, it is important to understand and control their electronic bands at the nanoscale. Here, we show that depletion layer engineering allows designing the energetic band profiles and predicting the optoelectronic properties of MO NCs. This is achieved by shell thickness tuning of core–shell Sn:In 2 O 3 –In 2 O 3 NCs, resulting in multiple band bending and multi-modal plasmonic response. We identify the modification of the band profiles after the light-induced accumulation of extra electrons as the main mechanism of photodoping and enhance the charge storage capability up to hundreds of electrons per NC through depletion layer engineering. Our experimental results are supported by theoretical models and are transferable to other core-multishell systems as well. Surface states, and the combination of suitable materials, induce spatial gradients in the carrier density of doped metal oxide nanocrystals, affecting their electronic structure and plasmonic behavior. Here the authors demonstrate depletion layer engineering and control in ITO/In 2 O 3 core–shell nanocrystals by tuning the shell thickness or by photodoping.

Concrete conceptual knowledge is supported by a distributed neural network representing different semantic features according to the neuroanatomy of sensory and motor systems. If and how this framework applies to abstract knowledge is currently debated. Here we investigated the specific brain correlates of different abstract categories. After a systematic a priori selection of brain regions involved in semantic cognition, i.e. responsible of, respectively, semantic representations and cognitive control, we used a fMRI-adaptation paradigm with a passive reading task, in order to modulate the neural response to abstract (emotions, cognitions, attitudes, human actions) and concrete (biological entities, artefacts) categories. Different portions of the left anterior temporal lobe responded selectively to abstract and concrete concepts. Emotions and attitudes adapted the left middle temporal gyrus, whereas concrete items adapted the left fusiform gyrus. Our results suggest that, similarly to concrete concepts, some categories of abstract knowledge have specific brain correlates corresponding to the prevalent semantic dimensions involved in their representation.