The 25th Mediterranean Conference on Control and Automation

The 25th Mediterranean Conference on Control and Automation (MED 2017) was held on July 3-6, 2017 on the island of Malta. The first MED took place in 1993 in Chania, Greece, and a complete list of the locations of later MED conferences is available at www.med-control.org. The 2017 edition was held for the first time in Malta, at the University of Malta Valletta Campus. The campus is a 17th century baroque building endowed with striking historical frescoes, portraits, and architectural features that is also well equipped with modern conference facilities. The conference was organized under the auspices of the Mediterranean Control Association (MCA) and the technical cosponsorship of the IEEE Control Systems Society and the IEEE Robotics and Automation Society.peer-reviewe

Synchronous Versus Metachronous Metastatic Disease: Impact of Time to Metastasis on Patient Outcome-Results from the International Metastatic Renal Cell Carcinoma Database Consortium

BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) may present with primary metastases (synchronous disease) or develop metastases during follow-up (metachronous disease). The impact of time to metastasis on patient outcome is poorly characterised. OBJECTIVE: To characterise overall survival (OS) and time to treatment failure (TTF) based on time to metastasis in mRCC patients treated with targeted therapy (tyrosine kinase inhibitors [TKIs]). DESIGN, SETTING, AND PARTICIPANTS: We used the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare synchronous (metastases within ≤3 mo of initial diagnosis of cancer) versus metachronous disease (evaluated by >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr intervals). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS and TFF were assessed using Kaplan-Meier curves. Cox multivariable regressions analyses (MVAs) were adjusted for baseline factors. RESULTS AND LIMITATIONS: Of 7386 patients with mRCC treated with first-line TKIs, 3906 (53%) and 3480 (47%) had synchronous and metachronous metastasis, respectively. More patients with synchronous versus metachronous disease had higher T stage (T1-2: 19% vs 34%), N1 disease (21% vs 6%), presence of sarcomatoid differentiation (15.8% vs 7.9%), Karnofsky performance status <80 (25.9% vs 15.1%), anaemia (62.5% vs 42.3%), elevated neutrophils (18.9% vs 10.9%), elevated platelets (21.6% vs 11.4%), bone metastases (40.4% vs 29.8%), and IMDC poor risk (40.6% vs 11.3%). Synchronous versus metachronous disease by intervals >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr correlated with poor TTF (5.6 mo vs 7.3, 8.0, 10.8, and 13.3 mo, p <  0.0001) and poor OS (median 16.7 mo vs 23.8, 30.2, 34.8, and 41.7 mo, p <  0.0001). In MVAs, the adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.98 (0.90-1.06), 0.81 (0.73-0.91), 0.74 (0.68-0.81), and 0.60 (0.54-0.67), respectively, for OS (p <  0.0001), and 1.00 (reference), 0.99 (0.92-1.06), 0.98 (0.90-1.07), 0.83 (0.77-0.89), and 0.66 (0.60-0.72), respectively, for TTF (p <  0.0001). Data were collected retrospectively. CONCLUSIONS: Timing of metastases after initial RCC diagnosis may impact the outcomes from targeted therapy in mRCC. PATIENT SUMMARY: We looked at the impact of the timing of metastatic outbreak on survival outcomes in kidney cancer patients treated with targeted therapy. We found that the longer time to metastatic development was associated with improved outcome

Roles of Electrostatics and Conformation in Protein-Crystal Interactions

In vitro studies have shown that the phosphoprotein osteopontin (OPN) inhibits the nucleation and growth of hydroxyapatite (HA) and other biominerals. In vivo, OPN is believed to prevent the calcification of soft tissues. However, the nature of the interaction between OPN and HA is not understood. In the computational part of the present study, we used molecular dynamics simulations to predict the adsorption of 19 peptides, each 16 amino acids long and collectively covering the entire sequence of OPN, to the {100} face of HA. This analysis showed that there is an inverse relationship between predicted strength of adsorption and peptide isoelectric point (P<0.0001). Analysis of the OPN sequence by PONDR (Predictor of Naturally Disordered Regions) indicated that OPN sequences predicted to adsorb well to HA are highly disordered. In the experimental part of the study, we synthesized phosphorylated and non-phosphorylated peptides corresponding to OPN sequences 65–80 (pSHDHMDDDDDDDDDGD) and 220–235 (pSHEpSTEQSDAIDpSAEK). In agreement with the PONDR analysis, these were shown by circular dichroism spectroscopy to be largely disordered. A constant-composition/seeded growth assay was used to assess the HA-inhibiting potencies of the synthetic peptides. The phosphorylated versions of OPN65-80 (IC50 = 1.93 µg/ml) and OPN220-235 (IC50 = 1.48 µg/ml) are potent inhibitors of HA growth, as is the nonphosphorylated version of OPN65-80 (IC50 = 2.97 µg/ml); the nonphosphorylated version of OPN220-235 has no measurable inhibitory activity. These findings suggest that the adsorption of acidic proteins to Ca2+-rich crystal faces of biominerals is governed by electrostatics and is facilitated by conformational flexibility of the polypeptide chain

Deep sea tests of a prototype of the KM3NeT digital optical module

The first prototype of a photo-detection unit of the future KM3NeT neutrino telescope has been deployed in the deepwaters of the Mediterranean Sea. This digital optical module has a novel design with a very large photocathode area segmented by the use of 31 three inch photomultiplier tubes. It has been integrated in the ANTARES detector for in-situ testing and validation. This paper reports on the first months of data taking and rate measurements. The analysis results highlight the capabilities of the new module design in terms of background suppression and signal recognition. The directionality of the optical module enables the recognition of multiple Cherenkov photons from the same (40)Kdecay and the localisation of bioluminescent activity in the neighbourhood. The single unit can cleanly identify atmospheric muons and provide sensitivity to the muon arrival directions

Detection potential of the KM3NeT detector for high-energy neutrinos from the Fermi bubbles

A recent analysis of the Fermi Large Area Telescope data provided evidence for a high-intensity emission of high-energy gamma rays with a E 2 spectrum from two large areas, spanning 50 above and below the Galactic centre (the ‘‘Fermi bubbles’’). A hadronic mechanism was proposed for this gamma-ray emission making the Fermi bubbles promising source candidates of high-energy neutrino emission. In this work Monte Carlo simulations regarding the detectability of high-energy neutrinos from the Fermi bubbles with the future multi-km3 neutrino telescope KM3NeT in the Mediterranean Sea are presented. Under the hypothesis that the gamma-ray emission is completely due to hadronic processes, the results indicate that neutrinos from the bubbles could be discovered in about one year of operation, for a neutrino spectrum with a cutoff at 100 TeV and a detector with about 6 km3 of instrumented volume. The effect of a possible lower cutoff is also considered.Published7–141.8. Osservazioni di geofisica ambientaleJCR Journalrestricte

Expansion cone for the 3-inch PMTs of the KM3NeT optical modules

[EN] Detection of high-energy neutrinos from distant astrophysical sources will open a new window on the Universe. The detection principle exploits the measurement of Cherenkov light emitted by charged particles resulting from neutrino interactions in the matter containing the telescope. A novel multi-PMT digital optical module (DOM) was developed to contain 31 3-inch photomultiplier tubes (PMTs). In order to maximize the detector sensitivity, each PMT will be surrounded by an expansion cone which collects photons that would otherwise miss the photocathode. Results for various angles of incidence with respect to the PMT surface indicate an increase in collection efficiency by 30% on average for angles up to 45 degrees with respect to the perpendicular. Ray-tracing calculations could reproduce the measurements, allowing to estimate an increase in the overall photocathode sensitivity, integrated over all angles of incidence, by 27% (for a single PMT). Prototype DOMs, being built by the KM3NeT consortium, will be equipped with these expansion cones.This work is supported through the EU, FP6 Contract no. 011937, FP7 grant agreement no. 212252, and the Dutch Ministry of Education, Culture and Science.Adrián Martínez, S.; Ageron, M.; Aguilar, JA.; Aharonian, F.; Aiello, S.; Albert, A.; Alexandri, M.... (2013). Expansion cone for the 3-inch PMTs of the KM3NeT optical modules. Journal of Instrumentation. 8(3):1-19. https://doi.org/10.1088/1748-0221/8/03/T03006S1198