Optimization of the wavesax device: numerical modelling and ocean wave basin tests

The Wavesax device has been conceived to be installed in ports and harbours, in the Mediterranean sea. Therefore, two aspects are quite important: flexibility of the device to fit in different structural configurations and replication in a large number of units. Preliminary numerical modelling of the fixed component of the device has been performed using Computational Fluid Dynamics analysis (RANS-CFD model) and considering four regular wave conditions typical of the Mediterranean sea. Main issues to be considered in the first stage scale modelling analysis are the effective functionality of the device conception (scale 1:20), the optimization of the design and position of the device in terms of generated velocity gradients in the working section where the turbine blades are installed. The main parameters to be investigated, both with numerical modelling and ocean wave basin tests, are the pressure field in different sections of the device, water levels for different wave conditions and device sinking. Following the scale model test, the numerical model was calibrated and validated. The paper presents the results of the numerical simulations related to different configurations of the device, under typical Mediterranean wave climates

Heterogeneity of neuroinflammatory responses in amyotrophic lateral sclerosis: A challenge or an opportunity?

Amyotrophic Lateral Sclerosis (ALS) is a complex pathology: (i) the neurodegeneration is chronic and progressive; it starts focally in specific central nervous system (CNS) areas and spreads to different districts; (ii) multiple cell types further than motor neurons (i.e., glial/immune system cells) are actively involved in the disease; (iii) both neurosupportive and neurotoxic neuroinflammatory responses were identified. Microglia cells (a key player of neuroinflammation in the CNS) attracted great interest as potential target cell population that could be modulated to counteract disease progression, at least in preclinical ALS models. However, the heterogeneous/multifaceted microglia cell responses occurring in different CNS districts during the disease represent a hurdle for clinical translation of single-drug therapies. To address this issue, over the past ten years, several studies attempted to dissect the complexity of microglia responses in ALS. In this review, we shall summarize these results highlighting how the heterogeneous signature displayed by ALS microglia reflects not only the extent of neuronal demise in different regions of the CNS, but also variable engagement in the attempts to cope with the neuronal damage. We shall discuss novel avenues opened by the advent of single-cell and spatial transcriptomics technologies, underlining the potential for discovery of novel therapeutic targets, as well as more specific diagnostic/prognostic not-invasive markers of neuroinflammation

Assessing residual hydropower potential of the La Plata Basin accounting for future user demands

La Plata Basin is shared by five countries (Argentina, Bolivia, Brazil, Paraguay and Uruguay), which have fast growing economies in South America. These countries need energy for their sustainable development; hence, hydropower can play a very important role as a renewable clean source of energy. This paper presents an analysis of the current hydropower production and electricity demand in La Plata Basin (LPB), and it analyses the maximum and residual hydropower potential of the basin for a horizon of 30 yr (i.e. year 2040). Current hydropower production is estimated based on historical available data, while future energy production is deduced from the available water in the catchment (estimated based on measured hydrographs of the past years), whereas electricity demand is assessed by correlating existing electricity demand with the estimated population growth and economic development. The maximum and residual hydropower potential of the basin were assessed for the mean annual flows of the present hydrological regime (1970–2000) and topographical characteristics of the area. <br><br> Computations were performed using an integrated GIS environment called VAPIDRO-ASTE released by the Research on Energy System (Italy). The residual hydropower potential of the basin is computed considering first that the water supply needs for population, industry and agriculture are served, and then hydropower energy is produced. The calculated hydropower production is found to be approximately half of the estimated electricity demand, which shows that there is a need to look for other sources of energy in the future

Synthesis and characterization of a “clickable” PBR28 TSPO-selective ligand derivative suitable for the functionalization of biodegradable polymer nanoparticles

Reactive microgliosis is a pathological hallmark that accompanies neuronal demise in many neurodegenerative diseases, ranging from acute brain/spinal cord injuries to chronic diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and age-related dementia. One strategy to assess and monitor microgliosis is to use positron emission tomography (PET) by exploiting radioligands selective for the 18 kDa translocator protein (TSPO) which is highly upregulated in the brain in pathological conditions. Several TSPO ligands have been developed and validated, so far. Among these, PBR28 has been widely adopted for PET imaging at both preclinical and clinical levels, thanks to its high brain penetration and high selectivity. For this reason, PBR28 represents a good candidate for functionalization strategies, where this ligand could be exploited to drive selective targeting of TSPO-expressing cells. Since the PBR28 structure lacks functional moieties that could be exploited for derivatization, in this work we explored a synthetic pathway for the synthesis of a PBR28 derivative carrying an alkyne group (PBR-alkyne), enabling the fast conjugation of the ligand through azide-alkyne cycloaddition, also known as click-chemistry. As a proof of concept, we demonstrated in silico that the derivatized PBR28 ligand maintains the capability to fit into the TSPO binding pocked, and we successfully exploited PBR-alkyne to decorate zwitterionic biodegradable polymer nanoparticles (NPs) resulting in efficient internalization in cultured microglia-like cell lines

Simultaneous flow cytometric characterization of multiple cell types retrieved from mouse brain/spinal cord through different homogenization methods

Recent advances in viral vector and nanomaterial sciences have opened the way for new cutting-edge approaches to investigate or manipulate the central nervous system (CNS). However, further optimization of these technologies would benefit from methods allowing rapid and streamline determination of the extent of CNS and cell-specific targeting upon administration of viral vectors or nanoparticles in the body. Here, we present a protocol that takes advantage of the high throughput and multiplexing capabilities of flow cytometry to allow a straightforward quantification of different cell subtypes isolated from mouse brain or spinal cord, namely microglia/macrophages, lymphocytes, astrocytes, oligodendrocytes, neurons and endothelial cells. We apply this approach to highlight critical differences between two tissue homogenization methods in terms of cell yield, viability and composition. This could instruct the user to choose the best method depending on the cell type(s) of interest and the specific application. This method is not suited for analysis of anatomical distribution, since the tissue is homogenized to generate a single-cell suspension. However, it allows to work with viable cells and it can be combined with cell-sorting, opening the way for several applications that could expand the repertoire of tools in the hands of the neuroscientist, ranging from establishment of primary cultures derived from pure cell populations, to gene-expression analyses and biochemical or functional assays on well-defined cell subtypes in the context of neurodegenerative diseases, upon pharmacological treatment or gene therapy

Assessing residual hydropower potential of the la Plata Basin accounting for future user demands

La Plata Basin is shared by five countries (Argentina, Bolivia, Brazil, Paraguay and Uruguay), which have fast growing economies in South America. These countries need energy for their sustainable development; hence, hydropower can play a very important role as a renewable clean source of energy. This paper presents an analysis of the current hydropower production and electricity demand in La Plata Basin (LPB), and it analyses the maximum and residual hydropower potential of the basin for a horizon of 30 yr (i.e. year 2040). Current hydropower production is estimated based on historical available data, while future energy production is deduced from the available water in the catchment (estimated based on measured hydrographs of the past years), whereas electricity demand is assessed by correlating existing electricity demand with the estimated population growth and economic development. The maximum and residual hydropower potential of the basin were assessed for the mean annual flows of the present hydrological regime (1970–2000) and topographical characteristics of the area. Computations were performed using an integrated GIS environment called VAPIDRO-ASTE released by the Research on Energy System (Italy). The residual hydropower potential of the basin is computed considering first that the water supply needs for population, industry and agriculture are served, and then hydropower energy is produced. The calculated hydropower production is found to be approximately half of the estimated electricity demand, which shows that there is a need to look for other sources of energy in the future