Despite the recognized potential of nanoparticles, only a few formulations have progressed to clinical trials, and an even smaller number have been approved by the regulatory authorities and ...marketed. Virus-like particles (VLPs) have emerged as promising alternatives to conventional nanoparticles due to their safety, biocompatibility, immunogenicity, structural stability, scalability, and versatility. Furthermore, VLPs can be surface-functionalized with small molecules to improve circulation half-life and target specificity. Through the functionalization and coating of VLPs, it is possible to optimize the response properties to a given stimulus, such as heat, pH, an alternating magnetic field, or even enzymes. Surface functionalization can also modulate other properties, such as biocompatibility, stability, and specificity, deeming VLPs as potential vaccine candidates or delivery systems. This review aims to address the different types of surface functionalization of VLPs, highlighting the more recent cutting-edge technologies that have been explored for the design of tailored VLPs, their importance, and their consequent applicability in the medical field.
The present study focuses on investigating the aerodynamic interaction between a three-element wing and wheel in ground effect, following the Formula One regulation change set for 2022, among which ...is the simplification of the front wing. This was accomplished by conducting a three-dimensional computational fluid dynamics analysis, using a Detached-Eddy Simulation approach, on a simplified one-quarter model of a Formula One racing car. The main goal was to examine how changing the front wing pressure distribution, by changing the incidence of the second flap, affected the wheel wake. The flow investigation indicated that the wheel wake is influenced by the flap configuration, which is mainly due to the fact that different flap configurations produce different upwash flow fields, leading to a variation of the separation point on top of the tire. As the separation point moves rearwards, the downwash generated in the central region (for a vertical plane) of the wheel wake increases incrementally, leading to a resultant wake that is shorter and further apart. The force investigation showed that the proximity between the region of instability (i.e., vortex breakdown) and the wing’s trailing edge influences the behavior of the transient oscillations, regarding the forces acting on the wing: detecting higher drag force fluctuations, when compared to downforce fluctuations.
•A novel stainless steel cuff was developed to connect GFRP I-section beams and columns.•Joints with different cuff thicknesses and lengths were tested under monotonic loading.•Ductility was ...registered taking advantage of the stainless steel material.•Marked pinching hindered the connection system’s ability to dissipate energy under cyclic loading.•The proposed cuff connection system was outperformed by (previously tested) flange cleated connection system.
This paper presents an experimental study about the monotonic and cyclic behaviour of beam-to-column connections between pultruded GFRP profiles with I-section, joined by means of stainless steel cuff connection parts. This study pursues a previous investigation by the authors in which custom stainless steel cuff parts were proposed for beam-to-column connections between pultruded tubular GFRP profiles, which presented very satisfactory performance under both monotonic and cyclic loading. A similar concept is now investigated for joining profiles with I-section shapes, which are more often used in civil engineering applications. Four series of full-scale beam-to-column connections were tested under monotonic loading, using stainless steel cuffs of two different plate thicknesses and lengths. The results show that higher cuff thickness and length provided higher initial stiffness and strength, with the cuff thickness being the most influential parameter. Conversely, the ductility of the connections decreased with increasing cuff thickness: the series with thinnest cuff parts presented the highest ductility. The series with the most ductile cuff part was also tested under cyclic loading and presented significant capacity to dissipate energy, but showed marked pinching. These results were compared to those of a stainless steel flange cleated connection system previously tested using the same GFRP I-section profiles: the connections using cuff parts presented worst mechanical behaviour than the cleated connections. This indicates that the cuff connection system is more efficient to join tubular sections than open sections, such as I-sections.
Abstract
This paper presents the first seismic tests on a full-scale all-composite frame structure, constituted by pultruded glass fiber–reinforced polymer (GFRP) profiles, to the best of the ...authors’ knowledge. These tests were performed in the scope of the FRP-Quake project, which aimed to provide an in-depth understanding of the dynamic and seismic behavior of all-GFRP structures, and to develop structural systems with adequate seismic resistance. Therefore, an extensive research program was conducted, from the material and component scales to the structural full-scale, which encompassed the development of appropriate beam-to-column bolted connection systems. The experimental campaign presented in this paper was composed of shaking table tests on a full-scale, two-story, three-dimensional (3D) frame of I section pultruded GFRP profiles connected with bolted stainless steel parts. First, modal identification tests were performed, which show the influence of adding floor masses, bracings, or both on the dynamic characteristics of the structure, which were accurately predicted with relatively simple linear finite-element (FE) models. Then, the frame structure was subjected to 18 base displacement histories with increasing intensity, which was based on the design earthquake for mainland Portugal. The results showed that the structure maintained its integrity for intensities up to 37% higher than the normative requirements. This showed the feasibility of using this type of all-GFRP structures in seismic areas.
New approaches aimed at identifying patient-specific drug targets and addressing unmet clinical needs in the framework of precision medicine are a strong motivation for researchers worldwide. As ...scientists learn more about proteins that drive known diseases, they are better able to design promising therapeutic approaches to target those proteins. The field of nanotechnology has been extensively explored in the past years, and nanoparticles (NPs) have emerged as promising systems for target-specific delivery of drugs. Virus-like particles (VLPs) arise as auspicious NPs due to their intrinsic properties. The lack of viral genetic material and the inability to replicate, together with tropism conservation and antigenicity characteristic of the native virus prompted extensive interest in their use as vaccines or as delivery systems for therapeutic and/or imaging agents. Owing to its simplicity and non-complex structure, one of the viruses currently under study for the construction of VLPs is the human immunodeficiency virus type 1 (HIV-1). Typically, HIV-1-based VLPs are used for antibody discovery, vaccines, diagnostic reagent development and protein-based assays. This review will be centered on the use of HIV-1-based VLPs and their potential biomedical applications.
Virus-like particles (VLPs) are nanoplatforms comprised of one or more viral proteins with the capacity to self-assemble without viral genetic material. VLPs arise as promising nanoparticles (NPs) ...that can be exploited as vaccines, as drug delivery vehicles or as carriers of imaging agents. Engineered antibody constructs, namely single-chain variable fragments (scFv), have been explored as relevant molecules to direct NPs to their target. A vector containing the scFv of an antibody, aimed at the human epidermal growth factor receptor 2 (HER2) and fused to the human immunodeficiency virus (HIV) protein gp41, was previously constructed. The work herein describes the early results concerning the production and the characterization of HIV-1-based VLPs expressing this protein, which could function as potential non-toxic tools for transporting drugs and/or imaging agents.
A major bottleneck in the successful development of central nervous system (CNS) drugs is the discovery and design of molecules that can cross the blood-brain barrier (BBB). Nano-delivery strategies ...are a promising approach that take advantage of natural portals of entry into the brain such as monoclonal antibodies (mAbs) targeting endogenous BBB receptors. However, the main selected mAbs rely on targeting broadly expressed receptors, such as the transferrin and insulin receptors, and in selection processes that do not fully mimic the native receptor conformation, leading to mistargeting and a low fraction of the administered dose effectively reaching the brain. Thus, there is an urgent need to identify new BBB receptors and explore novel antibody selection approaches that can allow a more selective delivery into the brain. Considering that in vitro models fail to completely mimic brain structure complexity, we explored an in vivo cell immunization approach to construct a rabbit derived single-domain antibody (sdAb) library towards BBB endothelial cell receptors. The sdAb antibody library was used in an in vivo phage display screening as a functional selection of novel BBB targeting antibodies. Following three rounds of selections, next generation sequencing analysis, in vitro brain endothelial barrier (BEB) model screenings and in vivo biodistribution studies, five potential sdAbs were identified, three of which reaching >0.6% ID/g in the brain. To validate the brain drug delivery proof-of-concept, the most promising sdAb, namely RG3, was conjugated at the surface of liposomes encapsulated with a model drug, the pan-histone deacetylase inhibitor panobinostat (PAN). The translocation efficiency and activity of the conjugate liposome was determined in a dual functional in vitro BEB-glioblastoma model. The RG3 conjugated PAN liposomes enabled an efficient BEB translocation and presented a potent antitumoral activity against LN229 glioblastoma cells without influencing BEB integrity. In conclusion, our in vivo screening approach allowed the selection of highly specific nano-antibody scaffolds with promising properties for brain targeting and drug delivery.
Beam-to-column connections are very relevant in the design of glass fibre reinforced polymer (GFRP) structures, since they can (i) govern the load capacity and robustness, presenting brittle failure ...modes, and (ii) reduce the deflections of GFRP flexural members. This paper presents a study about the mechanical behaviour of exterior beam-to-column connections between I-shaped pultruded GFRP profiles using stainless steel cleats. The main objective was to develop a connection system with non-corrodible auxiliary parts and improved ductility, by exploiting the stainless steel properties. For that, full-scale tests were performed to investigate (i) the monotonic response of nine different connection series, and (ii) the cyclic response of four of those series. The series differed in the number of bolts/rods (one or two bolt rows), cleat thickness (3, 6 and 8 mm), position of the cleats (flange or web) and use of column reinforcements, materialized by stainless steel rods and plates connecting the cleats to the columns’ back flange. All series that did not include such reinforcements presented tensile rupture at the columns’ web-flange junction at a very initial stage of the monotonic and cyclic tests, limiting the connections’ strength, ductility and capacity to dissipate energy. In the reinforced series, where this failure mode was avoided, the stiffness, strength, ductility and energy dissipation was highly influenced by the cleats thickness and bolts row number. The series that presented the best overall mechanical behaviour comprised 6 mm thick flange cleats, each with two bolt rows, and column reinforcements; in this series, the intermediate thickness of the cleats provided the best balance between the initial stiffness and non-linear deformation capacity, delaying GFRP local failure and allowing to mobilize the stainless steel ductility — this connection presented the highest strength and energy dissipation capacity. In addition to the experimental study presented herein, Part 2 (Martins et al., 2021) presents predictions of the stiffness and strength of the reinforced connection series using analytical and numerical methods.
•Full-scale exterior beam-to-column cleat connections were tested with and without column reinforcement.•Unreinforced connections performed poorly and their use in real applications is not recommended.•Significant non-linear behaviour was achieved by promoting yield of the stainless steel cleats.•The proposed connection system is able to dissipate energy under cyclic loading.•Stiffness and strength predictions are presented in Part 2.
The present work focuses on the prediction of initial stiffness and strength of bolted beam-to-column connections between pultruded glass fibre reinforced polymer (GFRP) profiles using stainless ...steel cleats — the first part (Martins et al., 2021) of this two-part paper presented an experimental study on the monotonic and cyclic behaviour of beam-to-column connections, while this second part focuses only on the monotonic behaviour of the reinforced connections. The initial stiffness was predicted using both analytical – via an adapted “component method” – and numerical models. The stiffness predictions compared well with experimental results. This study also identified the components with the highest influence on the connections’ stiffness, namely (i) the bending of the flange cleats and (ii) the transverse compression and shear of the columns’ webs. The strength of the reinforced connection series was predicted using a mixed analytical–numerical approach, as the local failure strengths were calculated in accordance with design standard recommendations, while the load distribution per connection component was computed through finite element (FE) models. The predicted failure modes and corresponding ultimate loads were in good agreement with the experimental tests. The proposed analytical and numerical models proved to be a viable tool for the design of GFRP structures, providing accurate predictions of the initial stiffness and strength of cleated connections.
•Connections’ initial stiffness was predicted with analytical and numerical models.•Component method, adapted for GFRPs behaviour, was used in analytical predictions.•The relative influence of each component to the overall stiffness was assessed.•Component strength was assessed with design guidance with load distribution from FE models.•Connections’ strength predictions agreed with experimental results.
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