Generation of large scale digital evaluation models via synthetic aperture radar interferometry

We investigate the possibility to generate a large-scale Digital Elevation Model by applying the Synthetic Aperture Radar interferometry technique and using tandem data acquired by the ERS-1/ERS-2 sensors. The presented study is mainly focused on the phase unwrapping step that represents the most critical point of the overall processing chain. In particular, we concentrate on the unwrapping problems related to the use of a large ERS tandem data set that, in order to be unwrapped, must be partitioned. The paper discusses the inclusion of external information (even rough) of the scene topography, the application of a region growing unwrapping technique and the insertion of possible constraints on the phase to be retrieved in order to minimize the global unwrapping errors. Our goal is the generation of a digital elevation model relative to an area of 300 km by 100km located in the southern part of Italy. Comparisons between the achieved result and a precise digital terrain model, relative to a smaller area, are also included

Supercontinent-paced magmatic destabilisation and recratonisation of the Yilgarn Craton

Knowledge of the evolution of ancient cratonic lithospheres underpins our understanding of Precambrian Earth. The Yilgarn Craton has exceptionally well-preserved Archean geology, with juvenile crust formation and major orogenesis concluding in the Neoarchean, and a stabilised upper-crustal architecture developing before 2.42 Ga. However, in an apparent dichotomy, geophysical models resolve lithospheric mantle composition outside the range of xenolith data from Archean regions, indicating the lithospheric mantle has since been extensively refertilised. Post-Archean igneous and sedimentary rocks record a prolonged lithospheric evolution that is not well resolved in datasets recording bulk crustal isotopic evolution. Reconciling these, we combine interpretation of geological and geophysical data to resolve two phases of lithosphere destabilisation driven by major magmatic events at ∼2.06 Ga and at ∼1.08 Ga. During destabilisation, sub-lithospheric and sub-crustal mantle fluxes caused extensive mantle refertilisation. For 200–400 Ma post-refertilisation, distributed sedimentary basins formed during recratonisation of the now denser lithosphere. The timing of these events suggests a relationship with the early stages of supercontinent assembly: Dominant downwelling beneath the assembling supercontinent sustains a sufficiently non-tensile tectonic setting to inhibit lithospheric thinning and breakup and enhances lateral flow of any upwelling mantle. This setting allows widespread intraplate refertilisation to occur while later the assembled supercontinent provides a stable setting allowing thermal re-equilibration and recratonisation to occur. In contrast, lithospheric refertilisation during supercontinent breakup will be more susceptible to density instabilities and recycling in later collisions. Consequently, we suggest that refertilisation of extant cratonic lithosphere may dominantly have occurred during the assembly of supercontinents

Amphiphilic CCK peptides assembled in supramolecular aggregates: structural investigations and in vitro studies

Supramolecular aggregates obtained by self-aggregation of five new cationic amphiphilic CCK8 peptides have been obtained in water solution and characterized for: (i) aggregate structure and stability; (ii) CCK8 peptide conformation and bioavailability on the external aggregate surface; and (iii) for their cell binding properties. The cationic amphiphilic CCK8 peptides self-aggregate giving a combination of liposomal and micelle structures, with radii ranging between B60 nm and B90 nm, and between B5 and B10 nm, respectively. The presence of CCK8 peptide well-exposed on the aggregate surface is demonstrated by fluorescence measurements. Peptide conformation changes in the five supramolecular aggregates: the CCK8 conformational behaviour is probably induced by the presence of three charged lysine residues close to the bioactive peptide sequence. Only aggregates in which the CCK8 peptide presents a structural arrangement similar to that found for the same peptide in DPC micelles give promising binding properties to CCK2-R receptors overexpressed by transfected A431 cells. Chemical modifications on the CCK8 N-terminus seem to play an important role in stabilizing the peptide active conformation, either when the peptide derivative is in monomeric or in aggregate form. For their easy preparation procedures and their binding properties, supramolecular aggregates based on cationic peptide amphiphiles can be considered as promising candidates for target selective drug carriers on cancer cells

Ruthenium(III) complexes entrapped in liposomes with enhanced cytotoxic and anti-metastatic properties

Metal-based anticancer drugs are pivotal in the fight against cancer pathologies. Since 1978 cis-platin was licensed for medical treatment of a wide number of tumor pathologies(1). However its chemiotherapic use is strongly limited by many and severe side effects and acquired tumor resistance. Since these limitations could be overcome by other metal complexes, in the last thirty years ruthenium compounds have been tested showing a remarkable antitumoral and antimetastatic activity associated with a lower toxicity. A hexacoordinate Ru(III) complex (NAMI-A) is currently undergoing advanced clinical evaluation (2). All data indicate that NAMI-A acts as a pro-drug, but the integrity of ruthenium complexes is essential to store the cytotoxic activity. In this scenario the condition of administration of ruthenium drugs are crucial to exploit their anticancer activity (3). In the last years innovative strategies have been produced to vehicle ruthenium ions in tumor cells like aggregates. This study aims to incorporate the ruthenium complexes in the inner aqueous compartment of liposomes and to test biological properties of two NAMI-A like pyridine derivatives. Specifically, we have investigated the pyridine derivatives of the sodium-compensated analogue of NAMI-A, Na[trans-RuCl4(pyridine)(DMSO)] (NAMI-Pyr) and Na[trans-RuCl4(Pytri)(DMSO)] (NAMI-Pytri). In thelatter complex the pyridine ligand is functionalized with a sugar moiety so as to increase biocompatibility and the ability to cross the cell membrane. The stability of the complexes was studied and compared in solution at different pH following UV-VIS spectra. Lipid formulations based on Egg PC were prepared adding Cholesterol, DSPE-PEG2000 joining molar ratio 57/38 /5% w/w respectively in MeOH/CHCl3 (50/50 v/v) mixture and hydrated with 0.9% w/w of NaCl. This composition was selected to reproduce analog supramolecular aggregates in clinical use to vehicle doxorubicin (Doxil). Ruthenium complexes were loaded into liposomes using the passive equilibration loading method. Full drug containing liposomes were structurally characterized by dynamic light scattering (DLS) measurements. Data indicate the formation of stable aggregates with size and shape in the right range for in vivo applications. The amount of encapsulated ruthenium complexes was quantified by means of ICP-AES. Stability and drug release properties of ruthenium containing liposomes were confirmed in buffer. The growth inhibitory effects of both liposomal and free complexes drug were tested on prostate cancer cells (PC3). Preliminary results show high cytotoxic effect of ruthenium complexes delivered by supramolecular aggregates with respect to free complexes drug

A Neural Networks Committee for the Contextual Bandit Problem

This paper presents a new contextual bandit algorithm, NeuralBandit, which does not need hypothesis on stationarity of contexts and rewards. Several neural networks are trained to modelize the value of rewards knowing the context. Two variants, based on multi-experts approach, are proposed to choose online the parameters of multi-layer perceptrons. The proposed algorithms are successfully tested on a large dataset with and without stationarity of rewards.Comment: 21st International Conference on Neural Information Processin

Nanostructures based on monoolein or diolein and amphiphilic gadolinium complexes as MRI contrast agents

Highly ordered two or three dimensional mesophases in aqueous solution could be usefully obtained by using monoolein (MO) or diolein (DO) monomers. Nanostructures (also indicated as nanoparticles, NPs) of MO or DO containing different amounts (1%, 5%, 10% and 20%) of the synthetic amphiphilic gadolinium complex (C18)2DTPA(Gd) have been prepared and characterized for their relaxometric and structural behaviors. The nanostructure is found in the 110–200 nm range for all investigated systems, while the presence of the gadolinium containing monomer produces a partial loss of the cubic symmetry, as shown by Cryo-TEM images of NPs doped with 10% w/w of (C18)2DTPA(Gd). Gadolinium containing nanostructures display high relaxivity values (in the 10–15 mM1 s1 range at 25 and 20 MHz, with a further increase at 37°C for DO based NPs), and interesting relaxometric properties for their possible use as MRI contrast agents. NPs containing 10% w/w of (C18)2DTPA(Gd) (MO3-NPs and DO3-NPs) have been also derivatized by introducing 3% wt of (C18)2–Peg3000–FA to obtain targeted aggregates (MO3-NP–FA, DO3-NP–FA). A preferential uptake efficiency of DO3-NP–FA in IGROV-1 cells with respect to DO-NPs without folic acid is observed, specially when cells are incubated with low concentrations of nanostructures or at short incubation times, thus indicating its potential use as a target-selective delivery system for MRI contrast agents on tumor cells overexpressing the folate receptor

Peptide-chelating agent conjugate for selective targeting of somatostatin receptor type1: Synthesis and characterization

Previously reported results suggest that the analogue of the somatostatin des-AA 1,2,5[D-Trp 8,IAmp 9]-somatostatin (CH-275) peptide bearing chelating agents able to coordinate radioactive metals could be used for scintigraphic imaging of tumor lesions overexpressing sstr1. An efficient synthetic procedure for the preparation of the somatostatin analogue CH-275 and its conjugate DTPAGlu-Gly-CH-275, bearing the chelating agent DTPAGlu (DTPAGlu = N,N-bis[2-[bis(carboxy-ethyl)amino]ethyl]-L-glutamic acid) on the N-terminus, by solid-phase peptide synthesis and 9-flourenymethyoxycarbonyl (Fmoc) chemistry, is here reported. Rapid and efficient labeling of DTPAGlu-Gly-CH-275 was achieved by addition of IIIIn(III) to the compound. Typical yields were greater than 97% as determined by reversed phase high performance liquid chromatography (HPLC) at specific activities in the range 4-9 GBq/μmol (100-250 Ci/mmol). A preliminary biological assay of the binding ability of IIIIn-DTPAGlu-Gly-CH-275 indicates, however, that the labeled compound does not display any specific interaction with somatostatin sstrl receptors in the tested cell lines. To confirm this unexpected negative result, competition binding experiments were carried out, in which fixed tracer amounts of the 125!-labeled somatostatin-14 were incubated with the receptor-expressing cells in the presence of DTPAGlu-Gly-CH-275 or CH-275 at concentrations ranging from 10 -10 to 10 -3 M. While CH-275 shows a IC 50 of 80 nM similar to that already found in displacement experiments on CHO-Kl sstrl-transfected cells, DTPAGlu-Gly-CH-275 displays instead very low or negligible affinity towards this receptor. The NMR solution characterization indicates that the presence of DTPAGlu does not influence the conformational and chemical features of the peptide moiety, thus suggesting that the loss in binding activity should be due to steric hindrance of either the chelating agent DTPAGlu or its indium comple

Performance Enhancement of Deep Reinforcement Learning Networks using Feature Extraction

The combination of Deep Learning and Reinforcement Learning, termed Deep Reinforcement Learning Networks (DRLN), offers the possibility of using a Deep Learning Neural Network to produce an approximate Reinforcement Learning value table that allows extraction of features from neurons in the hidden layers of the network. This paper presents a two stage technique for training a DRLN on features extracted from a DRLN trained on a identical problem, via the implementation of the Q-Learning algorithm, using TensorFlow. The results show that the extraction of features from the hidden layers of the Deep Q-Network improves the learning process of the agent (4.58 times faster and better) and proves the existence of encoded information about the environment which can be used to select the best action. The research contributes preliminary work in an ongoing research project in modeling features extracted from DRLNs

Short-term treatment with atorvastatin reduces platelet CD40 ligand and thrombin generation in hypercholesterolemic patients

Background - Soluble CD40L (sCD40L), a substance that maximally reflects in vivo platelet activation, is increased in patients with hypercholesterolemia. We investigated the relation between sCD40L and platelet CD4OL in hypercholesterolemic patients before and after a short-term treatment with atorvastatin. Methods and Results - Collagen-induced platelet CD40L and plasma levels of sCD40L and prothrombin fragment F1+2, a marker of thrombin generation, were investigated in 30 hypercholesterolemic patients and 20 healthy subjects. Hypercholesterolemic patients were then randomized to either diet ( n = 15; group A) or atorvastatin 10 mg/d ( group B); the aforementioned variables were measured at baseline and after 3 days of treatment. Compared with referents, hypercholesterolemic patients showed higher values of platelet CD40L ( P < 0.005), sCD40L ( P < 0.005), and F1 + 2 ( P < 0.003). Platelet CD40L was significantly correlated with sCD40L ( P < 0.001), and the latter was significantly correlated with F1 + 2 ( P < 0.001). The intervention trial showed no changes in group A but a significant decrease in platelet CD40L ( P < 0.01), sCD40L ( P < 0.002), and F1 + 2 ( P < 0.03) in group B. In vitro studies demonstrated that cholesterol enhanced platelet CD40L and CD40L-mediated clotting activation by human monocytes; also, atorvastatin dose-dependently inhibited platelet CD40L expression and clotting activation by CD40L-stimulated monocytes. Conclusions - This study shows that, in hypercholesterolemia, platelet overexpression of CD40L may account for enhanced plasma levels of sCD40L and F1 + 2. Atorvastatin exerts a direct antithrombotic effect via inhibition of platelet CD40L and CD40L-mediated thrombin generation, independently of its cholesterol-lowering effect