Abstract Current limitations of exogenous scaffolds or extracellular matrix based materials have underlined the need for alternative tissue-engineering solutions. Scaffolds may elicit adverse host ...responses and interfere with direct cell–cell interaction, as well as assembly and alignment of cell-produced ECM. Thus, fabrication techniques for production of scaffold-free engineered tissue constructs have recently emerged. Here we report on a fully biological self-assembly approach, which we implement through a rapid prototyping bioprinting method for scaffold-free small diameter vascular reconstruction. Various vascular cell types, including smooth muscle cells and fibroblasts, were aggregated into discrete units, either multicellular spheroids or cylinders of controllable diameter (300–500 μm). These were printed layer-by-layer concomitantly with agarose rods, used here as a molding template. The post-printing fusion of the discrete units resulted in single- and double-layered small diameter vascular tubes (OD ranging from 0.9 to 2.5 mm). A unique aspect of the method is the ability to engineer vessels of distinct shapes and hierarchical trees that combine tubes of distinct diameters. The technique is quick and easily scalable.
Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, ...a multitude of BRSV vaccines are used to reduce clinical signs. To enable the design of vaccination protocols to entirely stop virus circulation, we aimed to investigate the duration, character and efficacy of the immune responses induced by natural infections. The systemic humoral immunity was monitored every two months during two years in 33 dairy cattle in different age cohorts following a natural BRSV outbreak, and again in selected individuals before and after a second outbreak, four years later. Local humoral and systemic cellular responses were also monitored, although less extensively. Based on clinical observations and economic losses linked to decreased milk production, the outbreaks were classified as moderate. Following the first outbreak, most but not all animals developed neutralising antibody responses, BRSV-specific IgG1, IgG2 and HRSV F- and HRSV N-reactive responses that lasted at least two years, and in some cases at least four years. In contrast, no systemic T cell responses were detected and only weak IgA responses were detected in some animals. Seronegative sentinels remained negative, inferring that no new infections occurred between the outbreaks. During the second outbreak, reinfections with clinical signs and virus shedding occurred, but the signs were milder, and the virus shedding was significantly lower than in naïve animals. Whereas the primary infection induced similar antibody titres against the prefusion and the post fusion form of the BRSV F protein, memory responses were significantly stronger against prefusion F. In conclusion, even if natural infections induce a long-lasting immunity, it would probably be necessary to boost memory responses between outbreaks, to stop the circulation of the virus and limit the potential role of previously infected adult cattle in the chain of BRSV transmission.
A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved ...by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. In this study, we present data on safety and protective efficacy using sporozoites with deletions of two genes, that is the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, PbΔb9ΔslarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high-level protection. The human PfΔb9ΔslarpGAP generated without drug resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a PfΔb9ΔslarpSPZ vaccine.
To be competitive against other renewable energy sources, energy converted from the ocean waves needs to reduce its associated levelised cost of energy. It has been proven that advanced control ...algorithms can increase power production and device reliability. They act throughout the power conversion chain, from the hydrodynamics of wave absorption to the power take-off to improve the energy yield. The present work highlights the development and test of several algorithms to control the biradial turbine which is to be installed in the Mutriku oscillating water column plant. A collection of adaptive and predictive controllers is explored and both turbine speed controllers and latching strategies are examined. A Wave-to-Wire model of one chamber of the plant is detailed and simulation results of six control laws are obtained. The controllers are then validated using an electrical test infrastructure to prepare the future deployment in the plant. Finally, the control strategies are assessed against criteria like energy production, power quality or reliability.
•Comparative study and assessment of six control strategies developed for the biradial turbine in the Mutriku OWC plant.•Two are adaptive controllers, other two are latching controllers, one uses a RL scheme and one is a non-linear MPC.•Numerical simulations are done on a variety of sea states to support a performance and reliability analysis.•Significant performance improvement is brought by the RL model-free controller.•The MPC proved to bring the highest overall production.•Implementation and validation tests of the algorithms are performed via Hardware-In-the-Loop experimentations.
Improving the power production in wave energy plants is essential to lower the cost of energy production from this type of installations. Oscillating Water Column is among the most studied ...technologies to convert the wave energy into a useful electrical one. In this paper, three control algorithms are developed to control the biradial turbine installed in the Mutriku Wave Power Plant. The work presents a comparison of their main advantages and drawbacks first from numerical simulation results and then with practical implementation in the real plant, analysing both performance and power integration into the grid. The wave-to-wire model used to develop and assess the controllers is based on linear wave theory and adjusted with operational data measured at the plant. Three different controllers which use the generator torque as manipulated variable are considered. Two of them are adaptive controllers and the other one is a nonlinear Model Predictive Control (MPC) algorithm which uses information about the future waves to compute the control actions. The best adaptive controller and the predictive one are then tested experimentally in the real power plant of Mutriku, and the performance analysis is completed with operational results. A real time sensor installed in front of the plant gives information on the incoming waves used by the predictive algorithm. Operational data are collected during a two-week testing period, enabling a thorough comparison. An overall increase over 30% in the electrical power production is obtained with the predictive control law in comparison with the reference adaptive controller.
•Development and tuning of the Wave-to-Wire model of the Mutriku plant with field data.•Design of three control algorithms for the biradial turbine including a nonlinear MPC.•Numerical results show significant improvement in performance with the MPC.•Sea trials results confirm the good performance and reliable operation of the MPC.
Achieving safe and protective vaccination against respiratory syncytial virus (RSV) in infants and in calves has proven a challenging task. The design of recombinant antigens with a conformation ...close to their native form in virus particles is a major breakthrough. We compared two subunit vaccines, the bovine RSV (BRSV) pre-fusion F (preF) alone or with nanorings formed by the RSV nucleoprotein (preF+N). PreF and N proteins are potent antigenic targets for neutralizing antibodies and T cell responses, respectively. To tackle the challenges of neonatal immunization, three groups of six one-month-old calves with maternally derived serum antibodies (MDA) to BRSV received a single intramuscular injection of PreF, preF+N with Montanide
ISA61 VG (ISA61) as adjuvant or only ISA61 (control). One month later, all calves were challenged with BRSV and monitored for virus replication in the upper respiratory tract and for clinical signs of disease over one week, and then post-mortem examinations of their lungs were performed. Both preF and preF+N vaccines afforded safe, clinical, and virological protection against BRSV, with little difference between the two subunit vaccines. Analysis of immune parameters pointed to neutralizing antibodies and antibodies to preF as being significant correlates of protection. Thus, a single shot vaccination with preF appears sufficient to reduce the burden of BRSV disease in calves with MDA.
The induction of long-lasting clinical and virological protection is needed for a successful vaccination program against the bovine respiratory syncytial virus (BRSV). In this study, calves with ...BRSV-specific maternally derived antibodies were vaccinated once, either with (i) a BRSV pre-fusion protein (PreF) and Montanide
ISA61 VG (ISA61,
= 6), (ii) BRSV lacking the SH gene (ΔSHrBRSV,
= 6), (iii) a commercial vaccine (CV,
= 6), or were injected with ISA61 alone (
= 6). All calves were challenged with BRSV 92 days later and were euthanized 13 days post-infection. Based on clinical, pathological, and proteomic data, all vaccines appeared safe. Compared to the controls, PreF induced the most significant clinical and virological protection post-challenge, followed by ΔSHrBRSV and CV, whereas the protection of PreF-vaccinated calves was correlated with BRSV-specific serum immunoglobulin (Ig)G antibody responses 84 days post-vaccination, and the IgG antibody titers of ΔSHrBRSV- and CV-vaccinated calves did not differ from the controls on this day. Nevertheless, strong anamnestic BRSV- and PreF-specific IgG responses occurred in calves vaccinated with either of the vaccines, following a BRSV challenge. In conclusion, PreF and ΔSHrBRSV are two efficient one-shot candidate vaccines. By inducing a protection for at least three months, they could potentially improve the control of BRSV in calves.
Food integrity is a general term for sound, nutritive, healthy, tasty, safe, authentic, traceable, as well as ethically, safely, environment-friendly, and sustainably produced foods. In order to ...verify these properties, analytical methods with a higher degree of accuracy, sensitivity, standardization and harmonization and a harmonized system for their application in analytical laboratories are required. In this view, metrology offers the opportunity to achieve these goals. In this perspective article the current global challenges in food analysis and the principles of metrology to fill these gaps are presented. Therefore, the pan-European project METROFOOD-RI within the framework of the European Strategy Forum on Research Infrastructures (ESFRI) was developed to establish a strategy to allow reliable and comparable analytical measurements in foods along the whole process line starting from primary producers until consumers and to make all data
according to the FAIR data principles. The initiative currently consists of 48 partners from 18 European Countries and concluded its "Early Phase" as research infrastructure by organizing its future structure and presenting a proof of concept by preparing, distributing and comprehensively analyzing three candidate Reference Materials (rice grain, rice flour, and oyster tissue) and establishing a system how to compile, process, and store the generated data and how to exchange, compare them and make them accessible in data bases.
Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations ...with sporozoites that are attenuated by radiation (RAS) can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS) depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use.
Malaria sporozoites must first undergo intrahepatic development before a pathogenic blood-stage infection is established. The success of infection depends on host and parasite factors. In healthy ...human volunteers undergoing controlled human malaria infection (CHMI), we directly compared three clinical
isolates for their ability to infect primary human hepatocytes in vitro and to drive the production of blood-stage parasites in vivo. Our data show a correlation between the efficiency of strain-specific sporozoite invasion of human hepatocytes and the dynamics of patent parasitemia in study subjects, highlighting intrinsic differences in infectivity among
isolates from distinct geographical locales. The observed heterogeneity in infectivity among strains underscores the value of assessing the protective efficacy of candidate malaria vaccines against heterologous strains in the CHMI model.
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