Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for an ongoing human pandemic (COVID-19). There is a massive international effort underway to develop ...diagnostic reagents, vaccines, and antiviral drugs in a bid to slow down the spread of the disease and save lives. One part of that international effort involves the research community working with plants, bringing researchers from all over the world together with commercial enterprises to achieve the rapid supply of protein antigens and antibodies for diagnostic kits, and scalable production systems for the emergency manufacturing of vaccines and antiviral drugs. Here, we look at some of the ways in which plants can and are being used in the fight against COVID-19.
The current COVID-19 pandemic has created an immediate massive demand for diagnostic reagents based on SARS-CoV-2 RNA/proteins and corresponding antibodies, placing immense strain on the supply and distribution chain.Transient expression in plants could address the shortage by achieving rapid, larger-scale production, complemented by longer-term higher-volume production in transgenic plants.The same technology used to produce diagnostic reagents could also be used to produce vaccine candidates (SARS-CoV-2 subunits and virus-like particles) as well as therapeutic antibodies and antiviral proteins.It will be necessary to pool the international resources of molecular farming research groups and industry to capitalize on expertise, although distributed production using local infrastructure is the key to reaching all parts of the world.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A robust topology optimization approach is presented which uses the probabilistic first-order second-moment method for the estimation of mean value and variance of the compliance. The considered ...sources of uncertainty are the applied load, the spatially varying Young’s modulus, and the geometry with focus on the latter two. In difference to similar existing approaches for robust topology optimization, the presented approach requires only one solution of an adjoint system to determine the derivatives of the variance, which keeps the computation time close to the deterministic optimization. For validation, also the second-order fourth-moment method and Monte Carlo simulations are embedded into the optimization. For all approaches, the applicability and impact on the resulting design are demonstrated by application to benchmark examples. For random load, the first-order second-moment approach provides unsatisfying results. For random, Young’s modulus and geometry, however, the robust topology optimization using first-order second-moment approach provides robust designs at very little computational cost.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Recent press reports and complaints by hoteliers have called into question the credibility of travel-related user-generated content (UGC). Yet our understanding of the role of credibility perceptions ...in the context of UGC is limited, notwithstanding the rising interest in social media. Using an online survey of 661 travel consumers, this study applies the component-based structural equation modeling technique of partial least squares to examine online travelers’ perceptions of the credibility of UGC sources and how these perceptions influence attitudes and intentions toward UGC utilization in the travel planning process. The model also draws on the theory of homophily to make predictions about the antecedent of credibility. Results validate the Source Credibility Theory in the context of UGC but also accentuate the central mediating role of attitude. In addition, the study finds support for perceptual homophily as a critical determinant of both credibility and attitude. Theoretical and managerial implications are highlighted.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Efficacy of the Novel Cryoballoon
Introduction
The cryoballoon technology has the potential to isolate a pulmonary vein (PV) with a single energy application. However, using the first‐generation ...cryoballoon (CB‐1G) repeated freezing or additional focal ablation is often necessary. The novel second‐generation cryoballoon (CB‐2G) features a widened zone of optimal cooling comprising the whole frontal hemisphere. The aim of this study was to investigate the impact of the novel design on procedural efficacy of cryoballoon PV isolation (CB‐PVI).
Methods and Results
Single transseptal CB‐PVI using an endoluminal spiral mapping catheter was performed in 60 consecutive patients (CB‐1G, 28 mm, 300 seconds application time: 30 patients; CB‐2G, 28 mm, 240 seconds application time: 30 patients). When compared to the CB‐1G, using the CB‐2G increased single‐shot PVI rate from 51% to 84% (P < 0.001) and decreased procedure duration (128 ± 27 vs 98 ± 30 minutes; P < 0.001), and fluoroscopy exposure time (19.5 ± 7.4 vs 13.4 ± 5.3 min; P = 0.001). Effective CB‐2G PVI could be performed with increased real‐time PVI visualization rate (49% vs 76%; P < 0.001). Time to PVI (TPVI) was shorter in the CB‐2G group (79 ± 60 vs. 52 ± 36 seconds; P = 0.049). Procedure‐related complications occurred in 2 patients in the CB‐1G group and 1 patient in the CB‐2G group.
Conclusions
The CB‐2G significantly improved procedural efficacy compared to the CB‐1G and provided reliable TPVI measurement. TPVI may be used to adjust application time and number individually in future studies. Final conclusions regarding the safety profile of the CB‐2G requires additional research.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Despite the growing enthusiasm about social media, empirical research findings suggest that the majority of Internet users are not using consumer-generated media (CGM) for travel planning. Yet little ...is presently known about the relevant factors determining CGM usage for the specific purpose of travel planning. Using an online survey of travel consumers, this study investigates the intention to use consumer-generated media for travel planning by introducing new factors into the conventional TAM and using a partial least squares' estimation. Findings shed light on the differences in terms of the antecedents in this context. While the study demonstrates the theoretical validity and the empirical applicability of the TAM model to the context of CGM usage for travel planning, it goes further to verify the significant roles of distinctive factors like travelers' perceptions of similarity of interest, trustworthiness and enjoyment. Several managerial and research implications emerge.
► Found support for the conventional TAM related constructs in predicting intention. ► Observed differences in study's context regarding the nature of the relationships. ► Hedonic value is most influential in predicting the utilitarian use for trip planning. ► Findings support the appropriateness of the attitude construct in TAM research. ► Perceived similarity of interest wields a strong relationship with trustworthiness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Although plant biotechnology has been widely investigated for the production of clinical‐grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by ...pharmaceutical regulators for clinical testing. In the Pharma‐Planta project, the HIV‐neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant‐derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant‐derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first‐in‐human, double‐blind, placebo‐controlled, randomized, dose‐escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant‐derived pharmaceutical proteins.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Plant molecular pharming has emerged as a niche technology for the manufacture of pharmaceutical products indicated for chronic and infectious diseases, particularly for products that do not fit into ...the current industry-favored model of fermenter-based production campaigns. In this review, we explore the areas where molecular pharming can make the greatest impact, including the production of pharmaceuticals that have novel glycan structures or that cannot be produced efficiently in microbes or mammalian cells because they are insoluble or toxic. We also explore the market dynamics that encourage the use of molecular pharming, particularly for pharmaceuticals that are required in small amounts (such as personalized medicines) or large amounts (on a multi-ton scale, such as blood products and microbicides) and those that are needed in response to emergency situations (pandemics and bioterrorism). The impact of molecular pharming will increase as the platforms become standardized and optimized through adoption of good manufacturing practice (GMP) standards for clinical development, offering a new opportunity to produce inexpensive medicines in regional markets that are typically excluded under current business models.
Secretory IgA (SIgA) presents a promising avenue for mucosal immunotherapy yet faces challenges in expression, purification, and stability. IgA exists in two primary isotypes, IgA1 and IgA2, with ...IgA2 further subdivided into two common allotypes: IgA2m(1) and IgA2m(2). The major differences between IgA1 and IgA2 are located in the hinge region, with IgA1 featuring a 13-amino acid elongation that includes up to six O-glycosylation sites. Furthermore, the IgA2m(1) allotype lacks a covalent disulfide bond between heavy and light chains, which is present in IgA1 and IgA2m(2). While IgA1 demonstrates superior epitope binding and pathogen neutralization, IgA2 exhibits enhanced effector functions and stability against mucosal bacterial degradation. However, the noncovalent linkage in the IgA2m(1) allotype raises production and stability challenges. The introduction of distinct single mutations aims to facilitate an alternate disulfide bond formation to mitigate these challenges. We compare four different IgA2 versions with IgA1 to further develop secretory IgA antibodies against SARS-CoV-2 for topical delivery to mucosal surfaces. Our results indicate significantly improved expression levels and assembly efficacy of SIgA2 (P221R) in Nicotiana benthamiana. Moreover, engineered SIgA2 displays heightened thermal stability under physiological as well as acidic conditions and can be aerosolized using a mesh nebulizer. In summary, our study elucidates the benefits of stability-enhancing mutations in overcoming hurdles associated with SIgA expression and stability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Tree frogs have the remarkable ability to attach to smooth, rough, dry, and wet surfaces using their versatile toe pads. Tree frog attachment involves the secretion of mucus into the pad-substrate ...gap, requiring adaptations towards mucus drainage and pad lubrication. Here, we present an overview of tree frog attachment, with focus on (i) the morphology and material of the toe pad; (ii) the functional demands on the toe pad arising from ecology, lifestyle, and phylogenetics; (iii) experimental data of attachment performance such as adhesion and friction forces; and (iv) potential perspectives on future developments in the field. By revisiting reported data and observations, we discuss the involved mechanisms of attachment and propose new hypotheses for further research. Among others, we address the following questions: Do capillary and hydrodynamic forces explain the strong friction of the toe pads directly, or indirectly by promoting dry attachment mechanisms? If friction primarily relies on van der Waals (vdW) forces instead, how much do these forces contribute to adhesion in the wet environment tree frogs live in and what role does the mucus play? We show that both pad morphology and measured attachment performance suggest the coaction of several attachment mechanisms (e.g. capillary and hydrodynamic adhesion, mechanical interlocking, and vdW forces) with situation-dependent relative importance. Current analytical models of capillary and hydrodynamic adhesion, caused by the secreted mucus and by environmental liquids, do not capture the contributions of these mechanisms in a comprehensive and accurate way. We argue that the soft pad material and a hierarchical surface pattern on the ventral pad surface enhance the effective contact area and facilitate gap-closure by macro- to nanoscopic drainage of interstitial liquids, which may give rise to a significant contribution of vdW interactions to tree frog attachment. Increasing the comprehension of the complex mechanism of tree frog attachment contributes to a better understanding of other biological attachment systems (e.g. in geckos and insects) and is expected to stimulate the development of a wide array of bioinspired adhesive applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Over 700 patients with drug-refractory paroxysmal atrial fibrillation were randomly assigned to cryoballoon or radiofrequency ablation. Cryoballoon ablation was noninferior to radiofrequency for the ...composite of recurrent atrial arrhythmia, use of antiarrhythmic drugs, or repeat ablation.
According to a 2012 expert consensus statement, catheter ablation of drug-refractory paroxysmal atrial fibrillation is a class I level A indication,
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and pulmonary-vein isolation is the standard approach.
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The two most frequently used ablation technologies for pulmonary-vein isolation differ in the energy source and mode of application. The most common method is the use of radiofrequency current applied in a point-by-point mode, which leads to cellular necrosis by tissue heating; the other method is the use of cryogenic energy applied with a balloon in a single-step mode, which leads to necrosis by freezing (Figure 1). Radiofrequency ablation for atrial . . .
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