Unenhanced whole-body MRI versus PET-CT for the detection of prostate cancer metastases after primary treatment

The aim of this study was to evaluate the accuracy of unenhanced whole-body MRI, including whole-body Diffusion Weighted Imaging (DWI), used as a diagnostic modality to detect  pathologic lymph nodes and skeletal metastases in patients with prostate cancer (PCa) undergoing restaging after primary treatment

Liquid Metals Heat-Pipe solution for hypersonic air-intake leading edge: Conceptual design, numerical analysis and verification

Embedded propulsion systems will allow future hypersonic aircraft to reach amazing levels of performance. However, their peculiar small-radius air-intake leading edges pose serious challenges from the aerothermodynamic, design, integration, and manufacturing standpoints. This paper discloses the methodology developed in the framework of the H2020 STRATOFLY project and specifically tailored to support the conceptual and preliminary design phases of future high-speed transportation systems. The methodology implements an incremental approach which includes multifidelity design, modelling and simulation techniques. The specific application to the MR3, a Mach 8 waverider configuration with an embedded dorsal mounted propulsive subsystem, is reported. Different alternative solutions have been thoroughly analysed, including five liquid metals as fluids (Mercury, Cesium, Potassium, Sodium and Lithium) and relative wick and case materials (Steel, Titanium, Nickel, Inconel® and Tungsten) and three leading-edges materials (CMC, Tungsten with low emissivity painting and Tungsten with high emissivity painting). The analysis of the heat transfer limits (the capillary, entrainment, viscosity, chocking and boiling limits) carried out for all five fluids and relative compatible materials, together with a more accurate FEM analysis, suggest the adoption of a Nickel- Potassium liquid metal heat pipe completely integrated in a platelet air-intake leading edge made of CMC material. Ultimately, the effectiveness of the adopted solution throughout all mission phases has been verified with a detailed numerical model, built upon an electrical analogy

Aero-thermal design of STRATOFLY MR3 hypersonic vehicle

Civil hypersonic flights are one of the key technological challenges of next generation. The EC-funded STRATOFLY (Stratospheric Flying Opportunities for High-Speed Propulsion Concepts) project has the objective of assessing the potential of this type of high-speed transport vehicle to reach TRL6 by 2035, with respect to key technological, societal and economical aspects, namely thermal and structural integrity, low-emissions combined propulsion cycles, subsystems design and integration including smart energy management, environmental aspects impacting climate change, noise emissions and social acceptance, and economic viability accounting for safety and human factors. This paper presents the aerothermal design of the new STRATOFLY MR3 hypersonic vehicle

Thermal Protection System preliminary design of STRATOFLY high-speed propelled vehicle

This paper discloses the methodology and the preliminary results achieved in the framework of the H2020 STRATOFLY Project on the design of the Thermal Protection System of the MR3 vehicle. The results of the aero-thermal assessment performed throughout the trajectory clearly indicate the air-intake leading edges as the most critical area, thus dedicated Thermal Protection System alternatives have been explored. Specifically, solutions coupling high-temperature materials (mainly CMC and tungsten with different emissivity paints) with Liquid Metals Heat Pipe arrangements are modelled. Eventually, the effectiveness of the designed solutions is verified with detailed numerical simulation. The design which includes the air-intake main structure made of CMC material and integrating Nickel - Potassium heat pipe results to be the most promising solution to withstand the high thermal loads experienced by STRATOFLY MR3 throughout its Mach 8 long-haul route

Cooling system of STRATOFLY hypersonic vehicle: conceptual design, numerical analysis and verification

This paper describes the thermal design processes of STRATOFLY hypersonic vehicle cooling system showing either the methodology and the supporting FEM numerical simulations. It focuses on two different regions that are both subjected to severe overheating: air-intake leading edges and the combustion chamber. Final remarks on structure survivability are presented

Oral contraceptives combined with interferon β in multiple sclerosis

Objective: To test the effect of oral contraceptives (OCs) in combination with interferon b (IFN-b) on disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: One hundred fifty women with RRMS were randomized in a 1:1:1 ratio to receive IFNb-1a subcutaneously (SC) only (group 1), IFN-b-1a SC plus ethinylstradiol 20 mg and desogestrel 150 mg (group 2), or IFN-b-1a SC plus ethinylestradiol 40 mg and desogestrel 125 mg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures. Results: The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval [CI] 0.81–1.14) in group 1, 0.84 (95% CI 0.66–1.02) in group 2, and 0.72 (95% CI 0.53–0.91) in group 3, with a decrease of 14.1% (p 5 0.24) and 26.5% (p 5 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadoliniumenhancing lesions was greater in group 3 than in group 1 (p 5 0.03). No significant differences were detected in other secondary endpoints. IFN-b or OC discontinuations were equally distributed across groups. Conclusions: Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research

Preoperative staging of colorectal cancer using virtual colonoscopy: correlation with surgical results

The aim of this study was to evaluate the clinical usefulness of computed tomography colonography (CTC) in the preoperative staging in patients with abdominal pain for occlusive colorectal cancer (CRC) and to compare the results of CTC with the surgical ones

Transfection of the mutant MYH9 cDNA reproduces the most typical cellular phenotype of MYH9-related disease in different cell lines

ABSTRACT: BACKGROUND: Heterozygous mutations of MYH9, encoding the Non-Muscular Myosin Heavy Chain-IIA (NMMHC-IIA), cause a complex disorder named MYH9-related disease, characterized by a combination of different phenotypic features. At birth, patients present platelet macrocytosis, thrombocytopenia and leukocyte inclusions containing NMMHC-IIA. Moreover, later in life some of them develop the additional features of sensorineural hearing loss, cataracts and/or glomerulonephritis that sometimes leads to end stage renal failure. RESULTS: To clarify the mechanism by which the mutant NMMHC-IIA could cause phenotypic anomalies at the cellular level, we examined the effect of transfection of the full-length mutated D1424H MYH9 cDNAs. We have observed, by confocal microscopy, abnormal distribution of the protein and formation of rod-like aggregates reminiscent of the leukocyte inclusions found in patients. Co-transfection of differently labeled wild-type and mutant full-length cDNAs showed the simultaneous presence of both forms of the protein in the intracellular aggregates. CONCLUSION: These findings suggest that the NMMHC-IIA mutated in position 1424 is able to interact with the WT form in living cells, despite part of the mutant protein precipitates in non-functional aggregates. Transfection of the entire WT or mutant MYH9 in cell lines represents a powerful experimental model to investigate consequences of MYH9 mutations

Engineering the optical reflectance of randomly arranged self-assembled semiconductor nanowires

Metasurfaces made of arrays of vertically aligned semiconductor nanowires are suitable platforms for light management in optical and photonic applications. Here we report a design approach aimed at engineering the optical behavior of semiconductor nanowire ensembles randomly displaced on the substrate, in order to enhance modulation effects in their optical reflectance response. By resorting to analytical and numerical simulations we demonstrate that the combined implementation of a multi-shell layering together with a tapered designing on the individual nanowire offer new opportunities to tailor the optical reflectance oscillations in this kind of architectures. The simulation insights were compared to experimental results reported for self-assembled GaAs nanowires and GaAs/AlGaAs core-shell nanowires. The proposed approach is especially promising for epitaxially grown semiconductor nanowires, where the suggested design modifications can be easily implemented during the nanostructure growth

Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability. © 2013 European Molecular Biology Organization