259 research outputs found

    Numerical Modeling and Experimental Testing of a Pendulum Wave Energy Converter (PeWEC)

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    The research activities described in the present work aims to develop a pendulum converter (PeWEC: Pendulum Wave Energy Converter) for the Mediterranean Sea, where waves are shorter, thus with a higher frequency. In particular, the Pantelleria Island site wave climate is assumed as reference. The research activities started from the preliminary investigation of the working principle validity in the case of the Mediterranean Sea wave characteristics, taking into account a 1:45 scale prototype. The numerical model reliability and the success of experimental tests motivated the design and development of a 1:12 scaled device, useful for a deeper investigation of the technology capabilities and performances. Globally, the technology readiness level (TRL) was increased from 1 to 4. Important effort were focused in the development of a reliable model-based design and optimization methodology for the investigation of a full scale configuration. The latter was widely used to identify a preliminary full scale configuration and to assess the economic viability of the PeWEC technology in the Mediterranean Sea context. Results were benchmarked against the ISWEC pilot plant, deployed in 2015, in Pantelleria Island. One of the major outcomes of this analysis is a detailed overview of the advantages and drawbacks of an active (ISWEC) and a passive (PeWEC) technology, together with some guidelines for the improvement of this technology

    Post-transplant thrombotic microangiopathy due to a pathogenic mutation in complement factor I in a patient with membranous nephropathy: Case report and review of literature

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    Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury occurring due to endothelial cell damage and microthrombi formation in small vessels. TMA is primary when a genetic or acquired defect is identified, as in atypical hemolytic uremic syndrome (aHUS) or secondary when occurring in the context of another disease process such as infection, autoimmune disease, malignancy or drugs. Differentiating between a primary complement-mediated process and one triggered by secondary factors is critical to initiate timely treatment but can be challenging for clinicians, especially after a kidney transplant due to presence of multiple confounding factors. Similarly, primary membranous nephropathy is an immune-mediated glomerular disease associated with circulating autoantibodies (directed against the M-type phospholipase A2 receptor (PLA2R) in 70% cases) while secondary membranous nephropathy is associated with infections, drugs, cancer, or other autoimmune diseases. Complement activation has also been proposed as a possible mechanism in the etiopathogenesis of primary membranous nephropathy; however, despite complement being a potentially common link, aHUS and primary membranous nephropathy have not been reported together. Herein we describe a case of aHUS due to a pathogenic mutation in complement factor I that developed after a kidney transplant in a patient with an underlying diagnosis of PLA2R antibody associated-membranous nephropathy. We highlight how a systematic and comprehensive analysis helped to define the etiology of aHUS, establish mechanism of disease, and facilitated timely treatment with eculizumab that led to recovery of his kidney function. Nonetheless, ongoing anti-complement therapy did not prevent recurrence of membranous nephropathy in the allograft. To our knowledge, this is the first report of a patient with primary membranous nephropathy and aHUS after a kidney transplant

    Structure of Coagulation Factor II: Molecular Mechanism of Thrombin Generation and Development of Next-Generation Anticoagulants

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    Coagulation factor II, or prothrombin, is a multi-domain glycoprotein that is essential for life and a key target of anticoagulant therapy. In plasma, prothrombin circulates in two forms at equilibrium, “closed” (~80%) and “open” (~20%), brokered by the flexibility of the linker regions. Its structure remained elusive until recently when our laboratory solved the first X-ray crystal structure of the zymogen locked in the predominant closed form. Because of this technical breakthrough, fascinating aspects of the biology of prothrombin have started to become apparent, and with this, novel and important questions arise. Here, we examine the significance of the “closed”/“open” equilibrium in the context of the mechanism of thrombin generation. Further, we discuss the potential translational opportunities for the development of next-generation anticoagulants that arise from this discovery. By providing a structural overview of each alternative conformation, this minireview also offers a relevant example of modern structural biology and establishes a practical workflow to elucidate the structural features of analogous clotting and complement factors

    Traces in the desert: use of new technologies for the study and valorization of the Pachacamac sanctuary—Lima, Peru

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    Abstract Through time, the large ceremonial centers of the Peruvian pre-Hispanic coast have played an important role as Pachacamac, renowned for its famous oracle, which was an important site for cult and pilgrimage, where the use of water entered largely into ritual functions during Inca age and before. The sanctuary's landscape included sea, valley and lomas (ecosystem of grassy, seasonal knolls), and a complex and elaborate system of springs and canals which seem to use both the natural water table and the waters of the nearby Lurin river. In this sacred landscape there are over fifty buildings associated to springs and canals, built during a long occupation spanning over a 1000 years. This entire system must have been connected to Urpiwachaq lagoon, located to the northeast and only a few kilometers away from the sea. The origins of the lagoon and its relationship with the archaeological site evoke creation myths for the waters and marine species of the central coast. In this paper we discussed the results obtained from the geophysical investigations performed to define the water management system in the sanctuary and their connection with the lagoon. In particular, geo-electric, geomagnetic and ground penetrating radar prospections were carried out in the monumental area to determine the trajectory of the waters that drained into the lagoon from a series of ponds and canals. The interdisciplinary work in both the lagoon and monumental area provided a valuable source of information useful to better understand the history and function of the Pachacamac sanctuary in prehispanic times

    Wave Tank Testing of a Pendulum Wave Energy Converter 1:12 Scale Model

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    Wave Energy is a widespread, reliable renewable energy source. The early study on Wave Energy dates back in the 70's, with a particular effort in the last and present decade to make Wave Energy Converters (WECs) more profitable and predictable. The PeWEC (Pendulum Wave Energy Converter) is a pendulum-based WEC. The research activities described in the present work aim to develop a pendulum converter for the Mediterranean Sea, where waves are shorter, thus with a higher frequency compared to the ocean waves, a characteristic well agreeing with the PeWEC frequency response. The mechanical equations of the device are developed and coupled with the hydrodynamic Cummins equation. The work deals with the design and experimental tank test of a 1:12 scale prototype. The experimental data recorded during the testing campaign are used to validate the numerical model previously described. The numerical model proved to be in good agreement with the experiments

    Long-term physical impairments in survivors of COVID-19-associated ARDS compared with classic ARDS: A two-center study

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    Purpose: This work aimed to compare physical impairment in survivors of classic ARDS compared with COVID-19-associated ARDS (CARDS) survivors. Material and methods: This is a prospective observational cohort study on 248 patients with CARDS and compared them with a historical cohort of 48 patients with classic ARDS. Physical performance was evaluated at 6 and 12 months after ICU discharge, using the Medical Research Council Scale (MRCss), 6-min walk test (6MWT), handgrip dynamometry (HGD), and fatigue severity score (FSS). We also assessed activities of daily living (ADLs) using the Barthel index. Results: At 6 months, patients with classic ARDS had lower HGD (estimated difference [ED]: 11.71 kg, p < 0.001; ED 31.9% of predicted value, p < 0.001), 6MWT distance (ED: 89.11 m, p < 0.001; ED 12.96% of predicted value, p = 0.032), and more frequent significant fatigue (OR 0.35, p = 0.046). At 12 months, patients with classic ARDS had lower HGD (ED: 9.08 kg, p = 0.0014; ED 25.9% of predicted value, p < 0.001) and no difference in terms of 6MWT and fatigue. At 12 months, patients with classic ARDS improved their MRCss (ED 2.50, p = 0.006) and HGD (ED: 4.13 kg, p = 0.002; ED 9.45% of predicted value, p = 0.005), while those with CARDS did not. Most patients in both groups regained independence in ADLs at 6 months. COVID-19 diagnosis was a significant independent predictor of better HGD (p < 0.0001) and 6MWT performance (p = 0.001), and lower prevalence of fatigue (p = 0.018). Conclusions: Both classic ARDS and CARDS survivors experienced long-term impairments in physical functioning, confirming that post-intensive care syndrome remains a major legacy of critical illness. Surprisingly, however, persisting disability was more common in survivors of classic ARDS than in CARDS survivors. In fact, muscle strength measured with HGD was reduced in survivors of classic ARDS compared to CARDS patients at both 6 and 12 months. The 6MWT was reduced and fatigue was more common in classic ARDS compared to CARDS at 6 months but differences were no longer significant at 12 months. Most patients in both groups regained independent function in ADLs at 6 months

    Differences among Three Branded Formulations of Hyaluronic Acid: Data from Environmental Scanning Electron Microscope Profile, Rheology Behavior and Biological Activity

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    Background: This study has analysed the viscosupplemental proprieties of three commercially available formulations of Hyaluronic Acid (HA) suspension (F1: Synvisc, Hylan G-F 20; F2: Hyalgan; F3: Donegal HA 2.0), which differ in composition, Molecular Weight (MW) and HA content. Methods: Analyses were conducted using rheology measurements and Environmental Scanning Electron Microscope (ESEM). The capacity of the three tested formulations to inhibit specific Metalloproteases (MMPs) was also evaluated. Results: F1 is the only sample showing viscoelastic properties but may have increased immunogenicity attributable to the subsequent chemical cross-linking process that enhances the MW. F2 and F3 show a lower viscosity compared to F1. F2 has the lowest viscosity at low shear rate, the lower independence from the oscillatory stress and a solution-like rheology behaviour. F3 display a solution behaviour. However, unlike F2, F3 crossover point falls in the middle of the frequency range of interest showing a considerable rheological behaviour. The internal structure of F3 (pseudo-spongy thick filaments) suggests that it has the ability to interact with a great water content. The crossover points of the examined samples clearly reveal their different rheological behaviour, allowing their classification in gel-like or solution-like materials. F3 has higher ability in inhibiting MMP- 2 and MMP-9 activity compared to F1 and F2, probably due to its specific MW and/or higher HA concentration. Conclusion: The three tested HA formulations differ in rheological properties and inhibition of MMP-2 and MMP-9 activity. F3 seems to be the most appropriate formulation for the treatment of osteoarthritis and rheumatoid arthritis

    The Endangered Sardinian Grass Snake: Distribution Update, Bioclimatic Niche Modelling, Dorsal Pattern Characterisation, and Literature Review

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    The Sardinian grass snake, Natrix helvetica cetti, is an endangered endemic snake subspecies with a restricted and highly fragmented geographic distribution. Information on its ecology and detailed geographic distribution are scarce and may negatively impact on its conservation status. Therefore, a literature review on its taxonomy, morphology, ecology, and conservation is presented here. Moreover, field records from the authors, citizen science and the existing literature provide an updated geographic distribution highlighting its presence within 13 new and 7 historic 10 x 10 km cells. Bioclimatic niche modelling was then applied to explore patterns of habitat suitability and phenotypic variation within N. h. cetti. The geographic distribution of the species was found to be positively correlated with altitude and precipitation values, whereas temperatures howed a negative correlation. Taken together, these outcomes may explain the snake’s presence, particularly in eastern Sardinia. In addition, analysis of distribution overlap with the competing viperine snake (N. maura) and the urodeles as possible overlooked trophic resources (Speleomantes spp. and Euproctus platycephalus) showed overlaps of 66% and 79%, respectively. Finally, geographical or bioclimatic correlations did not explain phenotypic variation patterns observed in this highly polymorphic taxon. Perspectives on future research to investigate N. h. cetti’s decline and support effective conservation measures are discussed
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