Induction of Functional Neovascularization by Combined VEGF and Angiopoietin-1 Gene Transfer Using AAV Vectors

Vectors based on the adeno-associated virus (AAV) deliver therapeutic genes to muscle and heart at high efficiency and maintain transgene expression for long periods of time. Here we report about the synergistic effect on blood vessel formation of AAV vectors expressing the 165 aa isoform of vascular endothelial growth factor (VEGF165), a powerful activator of endothelial cells, and of angiopoietin-1 (Ang-1), which is required for vessel maturation. High titer AAV-VEGF165 and AAV-Ang-1 vector preparations were injected either alone or in combination in the normoperfused tibialis anterior muscle of rats. Long term expression of VEGF165 determined massive cellular infiltration of the muscle tissues over time, with the formation of a large set of new vessels. Strikingly, some of the cells infiltrating the treated muscles were found positive for markers of activated endothelial precursors (VEGFR-2/KDR and Tie-2) and for c-kit, an antigen expressed by pluripotent bone marrow stem cells. Expression of VEGF165 eventually resulted in the formation of structured vessels surrounded by a layer of smooth muscle cells. Presence of these arteriolae correlated with significantly increased blood perfusion in the injected areas. Co-expression of VEGF165 with angiopoietin-1-which did not display angiogenic effect per se-remarkably reduced leakage of vessels produced by VEGF165 alone

Geometry and modeling of an active offshore thrust-related fold system: the Amendolara Ridge, Ionian Sea, southern Italy

On the Ionian Sea coast of southern Italy, spanning the transition from the Calabrian Arc to the Apennines, NE-directed motion of the thin-skinned frontal thrust belt of the Apennines toward the Apulian foreland reportedly ceased during the Early-Middle Pleistocene. The submarine extension of the frontal thrust belt is represented by the Amendolara ridge, which stretches for over 80 km to the SE beneath the Taranto Gulf. High-resolution marine geophysical data collected on the Amendolara ridge during the TEATIOCA_2011 cruise provided unequivocal constraints to assert active fault-related fold growth. Single-channel seismic (sparker) and acoustic CHIRP profiles, corroborated by multibeam mapping and shallow coring, form the novel dataset to constrain the near-bottom evolution. The new data were benchmarked to the crustal geometry by means of interpretation of existing multichannel seismic profiles

Improving total body irradiation with a dedicated couch and 3D-printed patient-specific lung blocks: A feasibility study

Introduction: Total body irradiation (TBI) is an important component of the conditioning regimen in patients undergoing hematopoietic stem cell transplants. TBI is used in very few patients and therefore it is generally delivered with standard linear accelerators (LINACs) and not with dedicated devices. Severe pulmonary toxicity is the most common adverse effect after TBI, and patient-specific lead blocks are used to reduce mean lung dose. In this context, online treatment setup is crucial to achieve precise positioning of the lung blocks. Therefore, in this study we aim to report our experience at generating 3D-printed patient-specific lung blocks and coupling a dedicated couch (with an integrated onboard image device) with a modern LINAC for TBI treatment. Material and methods: TBI was planned and delivered (2Gy/fraction given twice a day, over 3 days) to 15 patients. Online images, to be compared with planned digitally reconstructed radiographies, were acquired with the couch-dedicated Electronic Portal Imaging Device (EPID) panel and imported in the iView software using a homemade Graphical User Interface (GUI). In vivo dosimetry, using Metal-Oxide Field-Effect Transistors (MOSFETs), was used to assess the setup reproducibility in both supine and prone positions. Results: 3D printing of lung blocks was feasible for all planned patients using a stereolithography 3D printer with a build volume of 14.5×14.5×17.5 cm3. The number of required pre-TBI EPID-images generally decreases after the first fraction. In patient-specific quality assurance, the difference between measured and calculated dose was generally<2%. The MOSFET measurements reproducibility along each treatment and patient was 2.7%, in average. Conclusion: The TBI technique was successfully implemented, demonstrating that our approach is feasible, flexible, and cost-effective. The use of 3D-printed patient-specific lung blocks have the potential to personalize TBI treatment and to refine the shape of the blocks before delivery, making them extremely versatile

Clinical discussions in antithrombotic therapy management in patients with atrial fibrillation: a delphi consensus panel

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Geosystemics View of Earthquakes

Earthquakes are the most energetic phenomena in the lithosphere: their study and comprehension are greatly worth doing because of the obvious importance for society. Geosystemics intends to study the Earth system as a whole, looking at the possible couplings among the different geo-layers, i.e., from the earth’s interior to the above atmosphere. It uses specific universal tools to integrate different methods that can be applied to multi-parameter data, often taken on different platforms (e.g., ground,marine or satellite observations). Itsmain objective is to understand the particular phenomenon of interest from a holistic point of view. Central is the use of entropy, together with other physical quantities that will be introduced case by case. In this paper, we will deal with earthquakes, as final part of a long-term chain of processes involving, not only the interaction between different components of the Earth’s interior but also the coupling of the solid earth with the above neutral or ionized atmosphere, and finally culminating with the main rupture along the fault of concern. Particular emphasis will be given to some Italian seismic sequences.Publishedid 4121A. Geomagnetismo e PaleomagnetismoJCR Journa

Magnetic Field and Electron Density Data Analysis from Swarm Satellites Searching for Ionospheric Effects by Great Earthquakes: 12 Case Studies from 2014 to 2016

We analyse Swarm satellite magnetic field and electron density data one month before and one month after 12 strong earthquakes that have occurred in the first 2.5 years of Swarm satellite mission lifetime in the Mediterranean region (magnitude M6.1+) or in the rest of the world (M6.7+). The search for anomalies was limited to the area centred at each earthquake epicentre and bounded by a circle that scales with magnitude according to the Dobrovolsky’s radius. We define the magnetic and electron density anomalies statistically in terms of specific thresholds with respect to the same statistical quantity along the whole residual satellite track (|geomagnetic latitude| ≤ 50°, quiet geomagnetic conditions). Once normalized by the analysed satellite tracks, the anomalies associated to all earthquakes resemble a linear dependence with earthquake magnitude, so supporting the statistical correlation with earthquakes and excluding a relationship by chance.PublishedID 3711A. Geomagnetismo e PaleomagnetismoJCR Journa

Precursory worldwide signatures of earthquake occurrences on Swarm satellite data

The study of the preparation phase of large earthquakes is essential to understand the physical processes involved, and potentially useful also to develop a future reliable short-term warning system. Here we analyse electron density and magnetic field data measured by Swarm three-satellite constellation for 4.7 years, to look for possible in-situ ionospheric precursors of large earthquakes to study the interactions between the lithosphere and the above atmosphere and ionosphere, in what is called the Lithosphere-Atmosphere-Ionosphere Coupling (LAIC). We define these anomalies statistically in the whole space-time interval of interest and use a Worldwide Statistical Correlation (WSC) analysis through a superposed epoch approach to study the possible relation with the earthquakes. We find some clear concentrations of electron density and magnetic anomalies from more than two months to some days before the earthquake occurrences. Such anomaly clustering is, in general, statistically significant with respect to homogeneous random simulations, supporting a LAIC during the preparation phase of earthquakes. By investigating different earthquake magnitude ranges, not only do we confirm the well-known Rikitake empirical law between ionospheric anomaly precursor time and earthquake magnitude, but we also give more reliability to the seismic source origin for many of the identified anomalies.Publishedid 202872A. Fisica dell'alta atmosferaJCR Journa

A control theoretical DAMA algorithm in DVB-RCS satellite systems with QoS support

The paper presents a DAMA (Demand Assigned Multiple Access) algorithm for geostationary satellite systems, where the round trip time between the capacity request and the assignment is greater than the maximum tolerated packet queuing delay, in terms of Quality of Service (QoS). The objective of the algorithm proposed in this paper is to dynamically compute the capacity request according to the actual needs avoiding high transmission delays and increasing the link utilization. A control theory approach has been taken on: the satellite network has been modeled as a feedback system and a proper controller has been introduced, in order to perform a control strategy that dynamically computes a target equilibrium and then steers the system towards such a target equilibrium. This work has been partially sponsored by the IST-SatSix project funded by European Commission within the 6th Framework Programme