Temperature-dependent morphology-electron mobility correlations of naphthalene diimide-indacenodithiophene copolymers prepared via direct arylation polymerization

A series of defect-free n-type copolymers poly(naphthalene diimide-alt-indacenodithiophene) P(NDI-IDT) comprising alternating naphthalene diimide (NDI) and indacenodithiophene (IDT) units is prepared using atom-economic direct arylation polycondensation (DAP)

Histone Deacetylase and Microtubules as Targets for the Synthesis of Releasable Conjugate Compounds

Design and synthesis of an HDAC inhibitor and its merger with three tubulin binders to create releasable conjugate compounds is described. The biological evaluation includes: a) in vitro reactivity with glutathione, b) antiproliferative activity, c) cell cycle analysis and d) quantification of protein acetylation. The cellular pharmacology study indicated that the HDAC-inhibitor-drug conjugates retained antimitotic and proapoptotic activity with a reduced potenc

Promising Non-cytotoxic Monosubstituted Chalcones to Target Monoamine Oxidase-B

A library of monosubstituted chalcones (1-17) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with 13 and 14 showing the best profiles. In particular, 13 exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B 13 binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas 14 is accommodated in the opposite way. The main conclusion of this cell biology, biochemistry, and structural study is to highlights 13 as a chalcone derivative that is worth consideration for the development of novel MAO-B-selective inhibitors for the treatment of neurodegenerative diseases

Requirement of a Membrane Potential for the Posttranslational Transfer of Proteins into Mitochondsria

Posttranslational transfer of most precursor proteins into mitochondria is dependent on energization of the mitochondria. Experiments were carried out to determine whether the membrane potential or the intramitochondrial ATP is the immediate energy source. Transfer in vitro of precursors to the ADP/ATP carrier and to ATPase subunit 9 into isolated Neurospora mitochondria was investigated. Under conditions where the level of intramitochondrial ATP was high and the membrane potential was dissipated, import and processing of these precursor proteins did not take place. On the other hand, precursors were taken up and processed when the intramitochondrial ATP level was low, but the membrane potential was not dissipated. We conclude that a membrane potential is involved in the import of those mitochondrial precursor proteins which require energy for intracellular translocatio

Intercomparison Exercise for Heavy Metals in PM10

The Joint Research Centre (JRC) has carried out an Intercomparison Exercise (IE) for the determination of heavy metals in particulate matter (PM10). The IE focussed on Lead (Pb), Arsenic (As), Nickel (Ni) and Cadmium (Cd), the heavy metals regulated by the 1st and 4th Daughter Directives for Air Pollution. Copper (Cu), Chromium (Cr) and Zinc (Zn), the elements included in the EMEP programme together with Aluminium (Al), Cobalt (Co), Iron (Fe), Manganese (Mn) and Vanadium (V) were also tested. Fourteen Laboratories, generally members of the Network of Air Quality Reference Laboratories (AQUILA), participated in the IE. The participants mainly used microwave digestion with nitric acid and hydrogen peroxide and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) or Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) for analysis as recommended in the reference method (EN 14902). However, a few participants used other methods: Energy Dispersive X-ray Fluorescence (EDXRF), Atomic Emission Spectrometry (ICP-AES) and Voltammetry for analysis and vaporisation on hot plate before microwave digestion, Soxhlet extraction, high pressure or cold Hydrogen Fluoride methods for digestion. Each participant received 5 samples to be analysed: a liquid sample prepared by dilution of a Certified Reference Material (CRM), a solution of a dust CRM sample digested by the JRC13F, a sub-sample of a dust CRM that each participating laboratory had to digest and analyse, a solution prepared by JRC after digestion of an exposed filter and a pair of filters (one blank filter and one exposed filter) to be digested and analysed by each participant. For 89 % of all types of samples, the DQOs of the 1st and 4th European Directives (uncertainty of 25 % for Pb and 40 % for As, Cd and Ni) were met. All together, this is a very good score. The best results were obtained for the liquid CRM, dust CRM digested by JRC, dust CRM and filter digested by JRC with 92, 90, 96 and 93 % of DQOs being met, respectively. It was found that the DQOs were not met if the difference of acidity between test samples and participant calibration standards was high. Conversely, only 76 % of DQOs were met for the filter to be digested by each participant with (about 85 % for Cd and Ni, 73/64 % for Pb and As, the most difficult element to determine). The worst results were associated with special events: explosion in microwave oven during digestion for two participants, a wrong dilution factor used by one participant and a huge contamination in the blank filter for another participant. Among the two explosions, one of them was probably the effect of a lack of temperature control in the digestion vessel. For the other explosion, the microwave digestion and the digestion program advised by EN 14902 is to be questioned. Moreover, satisfactory results were obtained using Soxhlet extraction, high pressure method and cold Hydrogen Fluoride digestion methods which are not presented in EN 14902. The DQOs of As and Cd could not be met with EDXRF whose limit of detection was too high for these two elements and for Cd using Voltammetry which suffered a strong interference for this element. Regarding the methods of analysis, apart the points mentioned just before about EDXRF and Voltammetry, good results were observed using ICP-OES for Cd, Ni and Pb. A few discrepancies were also registered for GF-AAS and ICP-MS but they were created by the special events or acidity problem mentioned before. This shows that even though GF-AAS and ICP-MS are found suitable, the implementation by each participant may be responsible for important mistakes.JRC.H.4-Transport and air qualit

The future of Cybersecurity in Italy: Strategic focus area

This volume has been created as a continuation of the previous one, with the aim of outlining a set of focus areas and actions that the Italian Nation research community considers essential. The book touches many aspects of cyber security, ranging from the definition of the infrastructure and controls needed to organize cyberdefence to the actions and technologies to be developed to be better protected, from the identification of the main technologies to be defended to the proposal of a set of horizontal actions for training, awareness raising, and risk management

Challenges of future multimedia QoE monitoring for internet service providers

The ever-increasing network traffic and user expectations at reduced cost make the delivery of high Quality of Experience (QoE) for multimedia services more vital than ever in the eyes of Internet Service Providers (ISPs). Real-time quality monitoring, with a focus on the user, has become essential as the first step in cost-effective provisioning of high quality services. With the recent changes in the perception of user privacy, the rising level of application-layer encryption and the introduction and deployment of virtualized networks, QoE monitoring solutions need to be adapted to the fast changing Internet landscape. In this contribution, we provide an overview of state-of-the-art quality monitoring models and probing technologies, and highlight the major challenges ISPs have to face when they want to ensure high service quality for their customers

A high-throughput screening of a chemical compound library in ovarian cancer stem cells

This work was performed under the frame of COST Action collaboration (COST Action CM1106). The generous contribution of AIRC (The Italian Association for Cancer Research) IG14536 to G.D. is gratefully acknowledged. A.H. acknowledges support from the János Bolyai fellowship of the Hungarian Academy of Sciences.Background: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and to the development of drug resistance after a first platinum-based regimen. The presence of a specific population of “cancer stem cells” could be responsible of the relapse of the tumor, and of the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. Method: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. Results and conclusion: Interestingly there were compounds active only on stem cells, only on differentiated cells and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.PostprintPeer reviewe