Power system vulnerability is a key concern in modern societies and many efforts have been devoted to its analysis. The authors propose an extended topological approach, which can incorporate several ...important features of the power grids, such as flow paths, line flow limits and gen/load bus distribution. Also, a set of new metrics able to provide an assessment of the system vulnerability is defined. 'Net-ability' measures the aptitude of the grid in transmitting power from generation to load buses efficiently. 'Path redundancy' assesses the available redundancy in terms of paths in transmitting power from a generation to a load bus, based on entropy. Based on the previous two metrics, the authors introduce a third metric, the 'survivability', as a global metric to evaluate the aptitude of the network in assuring the possibility to match generation and demand in case of failures or attacks. The metrics proposed will be applied to different test systems and to a real-transmission system to illustrate their application and effectiveness.
•Electricity and electrification is a viable solution for the energy transition.•Electricity triangle assures a consistent framework for the energy transition.•Multifaceted benefits: energetic, ...environmental and socio-economic.•Conceptualization of a set of metrics for impact assessment.•A real case study (Italy) considering its evolution up to 2050.
Greenhouse gases along with pollution generated by the present energy paradigm widely based on fossil fuels are providing large impacts in terms of climate change and the health of human and biological systems at large. A shift in the energy paradigm, from fossil fuels to renewable energy, is urgently needed for nature and society. This is what we refer to as the energy transition. An old commodity – electricity – can play a new key role in the energy transition. That can happen through what we call the electricity triangle involving electricity generation from Renewable Energy Sources, exploitation of electricity as the main energy vector, and electrification of the final energy uses in all sectors. The possible deployment of the electricity triangle must be carefully assessed in all its possible implications, from technological, economic, societal and environmental perspectives. In this paper, we conceptualize the electricity triangle as a viable approach to the energy transition, and we propose a set of holistic metrics to assess its possible impacts. We apply the electricity triangle framework to the case of Italy based on sectorial studies on RES generation and electrification in building, industry and transport sectors. Our results indicate that Italy in 2050 has the potential to achieve 85.6% penetration of RES in its electricity supply, while 41%, 53% and 42% of the energy consumptions in transport, residential, and industry sectors will be electrified. Ultimately, this would lead to a 68% reduction in CO2 emissions compared to current levels.
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•A year-long analysis of malaria parasite transmission in highly endemic areas was undertaken.•The oocyst load in mosquitoes was higher than expected (average 10 ...oocysts/mosquitoes).•Using a transmission model we found the number of oocysts per infectious blood meal.•This number (single-feed infection load) varied with season from three to 24 oocysts.•Malaria prevalence in humans can be used to approximate the single-feed infection load.
The population dynamics of human to mosquito malaria transmission in the field has important implications for the genetics, epidemiology and control of malaria. The number of oocysts in oocyst-positive mosquitoes developing from a single, naturally acquired infectious blood meal (herein referred to as a single-feed infection load) greatly influences the efficacy of transmission blocking interventions but still remains poorly documented. During a year-long analysis of malaria parasite transmission in Burkina Faso we caught and dissected wild malaria vectors to assess Plasmodium oocyst prevalence and load (the number of oocysts counted in mosquitoes with detectable oocysts) and the prevalence of salivary gland sporozoites. This was compared with malaria endemicity in the human population, assessed in cross-sectional surveys. Data were analysed using a novel transmission mathematical model to estimate the per bite transmission probability and the average single-feed infection load for each location. The observed oocyst load and the estimated single-feed infection load in naturally infected mosquitoes were substantially higher than previous estimates (means ranging from 3.2 to 24.5 according to seasons and locations) and indicate a strong positive association between the single-feed infection load and parasite prevalence in humans. This work suggests that highly infected mosquitoes are not rare in the field and might have a greater influence on the epidemiology and genetics of the parasite, and on the efficacy of novel transmission blocking interventions.
Fluid administration to increase stroke volume index (SVi) is a cornerstone of haemodynamic resuscitation. We assessed the accuracy of SVi variation during a calibrated abdominal compression ...manoeuvre (ΔSVi-CAC) to predict fluid responsiveness in children.
Patients younger than 8 yr with acute circulatory failure, regardless of their ventilation status, were selected. SVi, calculated as the average of five velocity–time integrals multiplied by the left ventricular outflow tract surface area, was recorded at four different steps: baseline, after an abdominal compression with a calibrated pressure of 25 mm Hg, after return to baseline, and then after a volume expansion (VE) of 10 ml kg−1 lactated Ringer solution over 10 min. Patients were classified as responders if SVi variation after volume expansion (ΔSVi-VE) increased by at least 15%.
The 39 children included had a median inter-quartile range (IQR) age of 9 5–31 months. Twenty patients were fluid responders and 19 were non-responders. ΔSVi-CAC correlated with ΔSVi-VE (r=0.829; P<0.001). The area under the receiver operating characteristic curve (ROCAUC) was 0.94 95% confidence interval (CI), 0.85–0.99. The best threshold for ΔSVi-CAC was 11% with a specificity of 95% 95% CI, 84–100 and a sensitivity of 75% 95% CI, 55–95. ROCAUC of respiratory variation of IVC diameter (ΔIVC) was 0.53 95% CI, 0.32–0.72.
ΔSVi-CAC during abdominal compression was a reliable method to predict fluid responsiveness in children with acute circulatory failure regardless of their ventilation status.
CPP Lyon sud est II: n° ANSM 2015-A00388-41 Clinicaltrial.gov: NCT02505646.
We have designed new basic amphiphilic peptides, ppTG1 and ppTG20 (20 amino acids), and evaluated their efficiencies in vitro and in vivo as single-component gene transfer vectors. ppTG1 and ppTG20 ...bind to nucleic acids and destabilize liposomes consisting of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and cholesterol (3:1 mol/mol) at pH 5 and pH 7. Complexes of plasmid DNA and ppTG1 gave rise to efficient transfection in a variety of human and murine cell lines at low charge ratios (+/- between 1 and 2). In cell culture experiments, such vectors were superior to the membrane-destabilizing peptide KALA. In comparison with cationic lipid-, dendrimer-, and polymer-based transfection agents like Superfect, polyethylenimine (PEI), and Lipofectin, ppTG1 vectors showed good transfection efficiencies, especially at low DNA doses. Moreover, we demonstrated for the first time successful gene transfer in living animals with a single-component peptide vector. In the mouse, intravenous injection of a luciferase expression plasmid complexed with ppTG1 or ppTG20 led to significant gene expression in the lung 24 hours after injection. Structure-function studies with ppTG1, ppTG20, and sequence variants suggest that the high gene transfer activity of these peptides is correlated with their propensity to exist in alpha-helical conformation, which seems to be strongly influenced by the nature of the hydrophobic amino acids.
With the increasing interest in vaccines to interrupt malaria transmission, there is a demand for harmonization of current methods to assess Plasmodium transmission in laboratory settings. Potential ...vaccine candidates are currently tested in the standard membrane feeding assay (SMFA) that commonly relies on Anopheles stephensi mosquitoes. Other mosquito species including Anopheles gambiae are the dominant malaria vectors for Plasmodium falciparum in sub-Saharan Africa.
Using human serum and monoclonal pre-fertilization (anti-Pfs48/45) and post-fertilization (anti-Pfs25) antibodies known to effectively inhibit sporogony, we directly compared SMFA based estimates of transmission-reducing activity (TRA) for An. stephensi and An. gambiae mosquitoes.
In the absence of transmission-reducing antibodies, average numbers of oocysts were similar between An. gambiae and An. stephensi. Antibody-mediated TRA was strongly correlated between both mosquito species, and absolute TRA estimates for pre-fertilisation monoclonal antibodies (mAb) showed no significant difference between the two species. TRA estimates for IgG of naturally exposed individuals and partially effective concentrations of anti-Pfs25 mAb were higher for An. stephensi than for An. gambiae.
Our findings support the use of An. stephensi in the SMFA for target prioritization. As a vaccine moves through product development, better estimates of TRA and transmission-blocking activity (TBA) may need to be obtained in epidemiologically relevant parasite-species combination.
The scaffolding protein insulin receptor tyrosine kinase substrate p53 (IRSp53), a ubiquitous regulator of the actin cytoskeleton, mediates filopodia formation under the control of Rho‐family ...GTPases. IRSp53 comprises a central SH3 domain, which binds to proline‐rich regions of a wide range of actin regulators, and a conserved N‐terminal IRSp53/MIM homology domain (IMD) that harbours F‐actin‐bundling activity. Here, we present the crystal structure of this novel actin‐bundling domain revealing a coiled‐coil domain that self‐associates into a 180 Å‐long zeppelin‐shaped dimer. Sedimentation velocity experiments confirm the presence of a single molecular species of twice the molecular weight of the monomer in solution. Mutagenesis of conserved basic residues at the extreme ends of the dimer abrogated actin bundling in vitro and filopodia formation in vivo, demonstrating that IMD‐mediated actin bundling is required for IRSp53‐induced filopodia formation. This study promotes an expanded view of IRSp53 as an actin regulator that integrates scaffolding and effector functions.
The two related members of the vasohibin family, VASH1 and VASH2, encode human tubulin detyrosinases. Here we demonstrate that, in contrast to VASH1, which requires binding of small vasohibin binding ...protein (SVBP), VASH2 has autonomous tubulin detyrosinating activity. Moreover, we demonstrate that SVBP acts as a bona fide activator of both enzymes. Phylogenetic analysis of the vasohibin family revealed that regulatory diversification of VASH-mediated tubulin detyrosination coincided with early vertebrate evolution. Thus, as a model organism for functional analysis, we used Trypanosoma brucei (Tb), an evolutionarily early-branched eukaryote that possesses a single VASH and encodes a terminal tyrosine on both α- and β-tubulin tails, both subject to removal. Remarkably, although detyrosination levels are high in the flagellum, TbVASH knockout parasites did not present any noticeable flagellar abnormalities. In contrast, we observed reduced proliferation associated with profound morphological and mitotic defects, underscoring the importance of tubulin detyrosination in cell division.
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•In contrast to VASH1, VASH2 does not require SVBP for detyrosinating activity•Diversification of tubulin detyrosination coincides with the appearance of vertebrates•TbVASH detyrosinates both α- and β-tubulin tails of Trypanosoma brucei•Parasites lacking TbVASH grow slowly and display severe morphological abnormalities
van der Laan et al. describe the evolutionary diversification of the VASH-mediated mechanism of tubulin detyrosination. In addition, they show that this modification plays an important role in Trypanosoma parasites, where it regulates cell division and cell morphology.
In the analysis of power systems security, recently a new concern related to possible malicious attacks caught much attention. Coordination among different transmission system operators (TSO) in an ...interconnected power system to counteract such attacks has become an important problem. This paper presents a general framework for describing the physical, cyber and decision-making aspects of the problem and their interrelations; within this framework, an analytic tool for the assessment of information impacts in handling on-line security after a malicious attack is proposed and discussed. The model is based on the socially rational multi-agent systems and the equilibrium of a fictitious play is considered to analyze the impacts of various levels of information available to the interconnected system operators on the outcomes of the decision-making process under attack. A 34-buses test system, with 3 systems interconnected by tie-lines, is presented to illustrate the model and compare the impacts of different information scenarios.
We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% ...of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.
We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.
No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10
) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.7095%CI 1.3-8.2, P = 2.1 × 10
). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.6595%CI 2.1-2635.4, P = 3.4 × 10
), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.409%CI 2.3-8.4, P = 7.7 × 10
). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age SD = 43.3 20.3 years) than the other patients (56.0 17.3 years; P = 1.68 × 10
).
Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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