132 research outputs found
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Seismic design of reinforced concrete frames for minimum embodied CO2 emissions
Optimum structural design of reinforced concrete (RC) frames has been the focus of extensive research. Typically, previous studies set economic cost as the main design objective despite the fact that RC structures are major contributors of CO2 emissions. The limited number of studies examining optimum design of RC frames for minimum CO2 emissions do not address seismic design considerations. However, in many countries around the world, including most of the top-10 countries in CO2 emissions from cement production, RC structures must be designed against earthquake threat. To bridge this gap, the present study develops optimum seismic designs of RC frames for minimum cradle to gate embodied CO2 emissions and compares them with optimum designs based on construction cost. The aim is to identify efficient design practices that minimize the environmental impact of earthquake-resistant RC frames and examine the trade-offs between their cost and CO2 footprint. To serve this goal, an RC frame is optimally designed according to all ductility classes of Eurocode 8 and for various design peak ground accelerations (PGAs), concrete classes and materials embodied CO2 footprint scenarios. It is found that the minimum feasible CO2 emissions of RC frames strongly depend on the adopted ductility class in regions of high seismicity, where low ductility seismic design can generate up to 60% more CO2 emissions than designs for medium and high ductility. The differences reduce, however, as the level of seismicity decreases. Furthermore, CO2 emissions increase significantly with the design PGA. On the other hand, they are less sensitive to the applied concrete class. It is also concluded that, for medium to high values of the ratio of the unit environmental impact of reinforcing steel to the respective impact of concrete, the minimum CO2 seismic designs are very closely related to the minimum cost designs. However, for low values of the same ratio, the minimum cost design solutions can generate up to 13% more emissions than the minimum CO2 designs
Targeted and non-targeted proteomics to characterize the parasite proteins of Echinococcus multilocularis metacestodes.
The larval stage of the cestode Echinococcus multilocularis is the causative agent of alveolar echinococcosis. To investigate the biology of these stages and to test novel compounds, metacestode cultures represent a suitable in vitro model system. These metacestodes are vesicles surrounded by an envelope formed by the vesicle tissue (VT), which is formed by the laminated and germinal layer, and filled with vesicle fluid (VF). We analyzed the proteome of VF and VT by liquid chromatography tandem mass spectrometry (LC-MS/MS) and identified a total of 2,954 parasite proteins. The most abundant protein in VT was the expressed conserved protein encoded by EmuJ_000412500, followed by the antigen B subunit AgB8/3a encoded by EmuJ_000381500 and Endophilin B1 (protein p29). In VF, the pattern was different and dominated by AgB subunits. The most abundant protein was the AgB8/3a subunit followed by three other AgB subunits. In total, the AgB subunits detected in VF represented 62.1% of the parasite proteins. In culture media (CM), 63 E. multilocularis proteins were detected, of which AgB subunits made up 93.7% of the detected parasite proteins. All AgB subunits detected in VF (encoded by EmuJ_000381100-700, corresponding to AgB8/2, AgB8/1, AgB8/4, AgB8/3a, AgB8/3b, and AgB8/3c) were also found in CM, except the subunit encoded by EmuJ_000381800 (AgB8/5) that was very rare in VF and not detected in CM. The relative abundance of the AgB subunits in VF and CM followed the same pattern. In VT, only the subunits EmuJ_000381500 (AgB8/3a) and EmuJ_000381200 (AgB8/1) were detected among the 20 most abundant proteins. To see whether this pattern was specific to VF from in vitro cultured metacestodes, we analyzed the proteome of VF from metacestodes grown in a mouse model. Here, the AgB subunits encoded by EmuJ_000381100-700 constituted the most abundant proteins, namely, 81.9% of total protein, with the same order of abundance as in vitro. Immunofluorescence on metacestodes showed that AgB is co-localized to calcareous corpuscles of E. multilocularis. Using targeted proteomics with HA-tagged EmuJ_000381200 (AgB8/1) and EmuJ_000381100 (AgB8/2), we could show that uptake of AgB subunits from CM into VF occurs within hours
Establishment and application of unbiased in vitro drug screening assays for the identification of compounds against Echinococcus granulosus sensu stricto.
Echinococcus multilocularis and E. granulosus s.l. are the causative agents of alveolar and cystic echinococcosis, respectively. Drug treatment options for these severe and neglected diseases are limited to benzimidazoles, which are not always efficacious, and adverse side effects are reported. Thus, novel and improved treatments are needed. In this study, the previously established platform for E. multilocularis in vitro drug assessment was adapted to E. granulosus s.s. In a first step, in vitro culture protocols for E. granulosus s.s. were established. This resulted in the generation of large amounts of E. granulosus s.s. metacestode vesicles as well as germinal layer (GL) cells. In vitro culture of these cells formed metacestode vesicles displaying structural characteristics of metacestode cysts generated in vivo. Next, drug susceptibilities of E. multilocularis and E. granulosus s.s. protoscoleces, metacestode vesicles and GL cells were comparatively assessed employing established assays including (i) metacestode vesicle damage marker release assay, (ii) metacestode vesicle viability assay, (iii) GL cell viability assay, and (iv) protoscolex motility assay. The standard drugs albendazole, buparvaquone, mefloquine, MMV665807, monepantel, niclosamide and nitazoxanide were included. MMV665807, niclosamide and nitazoxanide were active against the parasite in all four assays against both species. MMV665807 and monepantel were significantly more active against E. multilocularis metacestode vesicles, while albendazole and nitazoxanide were significantly more active against E. multilocularis GL cells. Albendazole displayed activity against E. multilocularis GL cells, but no effects were seen in albendazole-treated E. granulosus s.s. GL cells within five days. Treatment of protoscoleces with albendazole and monepantel had no impact on motility. Similar results were observed for both species with praziquantel and its enantiomers against protoscoleces. In conclusion, in vitro culture techniques and drug screening methods previously established for E. multilocularis were successfully implemented for E. granulosus s.s., allowing comparisons of drug efficacy between the two species. This study provides in vitro culture techniques for the reliable generation of E. granulosus s.s. metacestode vesicles and GL cell cultures and describes the validation of standardized in vitro drug screening methods for E. granulosus s.s
Targeted and non-targeted proteomics to characterize the parasite proteins of Echinococcus multilocularis metacestodes
The larval stage of the cestode Echinococcus multilocularis is the causative agent of alveolar echinococcosis. To investigate the biology of these stages and to test novel compounds, metacestode cultures represent a suitable in vitro model system. These metacestodes are vesicles surrounded by an envelope formed by the vesicle tissue (VT), which is formed by the laminated and germinal layer, and filled with vesicle fluid (VF). We analyzed the proteome of VF and VT by liquid chromatography tandem mass spectrometry (LC-MS/MS) and identified a total of 2,954 parasite proteins. The most abundant protein in VT was the expressed conserved protein encoded by EmuJ_000412500, followed by the antigen B subunit AgB8/3a encoded by EmuJ_000381500 and Endophilin B1 (protein p29). In VF, the pattern was different and dominated by AgB subunits. The most abundant protein was the AgB8/3a subunit followed by three other AgB subunits. In total, the AgB subunits detected in VF represented 62.1% of the parasite proteins. In culture media (CM), 63 E. multilocularis proteins were detected, of which AgB subunits made up 93.7% of the detected parasite proteins. All AgB subunits detected in VF (encoded by EmuJ_000381100–700, corresponding to AgB8/2, AgB8/1, AgB8/4, AgB8/3a, AgB8/3b, and AgB8/3c) were also found in CM, except the subunit encoded by EmuJ_000381800 (AgB8/5) that was very rare in VF and not detected in CM. The relative abundance of the AgB subunits in VF and CM followed the same pattern. In VT, only the subunits EmuJ_000381500 (AgB8/3a) and EmuJ_000381200 (AgB8/1) were detected among the 20 most abundant proteins. To see whether this pattern was specific to VF from in vitro cultured metacestodes, we analyzed the proteome of VF from metacestodes grown in a mouse model. Here, the AgB subunits encoded by EmuJ_000381100–700 constituted the most abundant proteins, namely, 81.9% of total protein, with the same order of abundance as in vitro. Immunofluorescence on metacestodes showed that AgB is co-localized to calcareous corpuscles of E. multilocularis. Using targeted proteomics with HA-tagged EmuJ_000381200 (AgB8/1) and EmuJ_000381100 (AgB8/2), we could show that uptake of AgB subunits from CM into VF occurs within hours
Dual inhibition of the Echinococcus multilocularis energy metabolism.
Alveolar echinococcosis is caused by the metacestode stage of the zoonotic parasite Echinococcus multilocularis. Current chemotherapeutic treatment options rely on benzimidazoles, which have limited curative capabilities and can cause severe side effects. Thus, novel treatment options are urgently needed. In search for novel targetable pathways we focused on the mitochondrial energy metabolism of E. multilocularis. The parasite relies hereby on two pathways: The classical oxidative phosphorylation including the electron transfer chain (ETC), and the anaerobic malate dismutation (MD). We screened 13 endochin-like quinolones (ELQs) in vitro for their activities against two isolates of E. multilocularis metacestodes and isolated germinal layer cells by the phosphoglucose isomerase (PGI) assay and the CellTiter Glo assay. For the five most active ELQs (ELQ-121, ELQ-136, ELQ-271, ELQ-400, and ELQ-437), EC50 values against metacestodes were assessed by PGI assay, and IC50 values against mammalian cells were measured by Alamar Blue assay. Further, the gene sequence of the proposed target, the mitochondrial cytochrome b, was analyzed. This allowed for a limited structure activity relationship study of ELQs against E. multilocularis, including analyses of the inhibition of the two functional sites of the cytochrome b. By applying the Seahorse XFp Extracellular Flux Analyzer, oxygen consumption assays showed that ELQ-400 inhibits the E. multilocularis cytochrome bc 1 complex under normoxic conditions. When tested under anaerobic conditions, ELQ-400 was hardly active against E. multilocularis metacestodes. These results were confirmed by transmission electron microscopy. ELQ-400 treatment increased levels of parasite-released succinate, the final electron acceptor of the MD. This suggests that the parasite switched to MD for energy generation. Therefore, MD was inhibited with quinazoline, which did not induce damage to metacestodes under anaerobic conditions. However, it reduced the production of succinate compared to control treated parasites (i.e., inhibited the MD). The combination treatment with quinazoline strongly improved the activity of the bc 1 inhibitor ELQ-400 against E. multilocularis metacestodes under anaerobic conditions. We conclude that simultaneous targeting of the ETC and the MD of E. multilocularis is a possible novel treatment approach for alveolar echinococcosis, and possibly also other foodborne diseases inflicted by platyhelminths, which cause substantial economic losses in livestock industry
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Contribution to sustainable seismic design of reinforced concrete members through embodied CO2 emissions optimization
The embodied CO2 emissions of reinforced concrete (RC) structures can be significantly reduced by structural optimization that maximizes structural efficiency. Previous studies dealing with design of RC structures for minimum CO2 emissions do not address seismic design provisions. This is the case despite the fact that in many countries around the world, including most of the top-10 countries in CO2 emissions from cement production, RC structures have to be designed against earthquake hazard. To fill a part of this gap, this study, using exhaustive search, examines optimum designs of RC beam and column members for minimum embodied CO2 emissions according to Eurocode-8 for all ductility classes and compares them with optimum designs based on material cost. It is shown that seismic designs for minimum CO2 footprint lead to less CO2 emissions but are more expensive than minimum cost designs. Their differences strongly depend on the assumed values of the environmental impact of reinforcing steel and concrete materials. Furthermore, it is concluded that seismic design for high ductility classes can drive to significant reductions in embodied CO2 emissions
Optimization Formulations for the Design of Low Embodied Energy Structures Made from Reused Elements
The building sector is one of the major contributors to material resource consumption, greenhouse gas emission and waste production. Load-bearing systems have a particularly large environmental impact because of their material and energy intensive manufacturing process. This paper aims to address the reduction of building structures environmental impacts through reusing structural elements for multiple service lives. Reuse avoids sourcing raw materials and requires little energy for reprocessing. However, to design a new structure reusing elements available from a stock is a challenging problem of combinatorial nature. This is because the structural system layout is a result of the available elements’ mechanical and geometric properties. In this paper, structural optimization formulations are proposed to design truss systems from available stock elements. Minimization of weight, cut-off waste and embodied energy are the objective functions subject to ultimate and serviceability constraints. Case studies focusing on embodied energy minimization are presented for: (1) three roof systems with predefined geometry and topology; (2) a bridge structure whose topology is optimized using the ground structure approach; (3) a geometry optimization to better match the optimal topology from 2 and available stock element lengths. In order to benchmark the energy savings through reuse, the optimal layouts obtained with the proposed methods are compared to weight-optimized solutions made of new material. For these case studies, the methods proposed in this work enable reusing stock elements to design structures embodying up to 71% less energy and hence having a significantly lower environmental impact with respect to structures made of new material
Structural sustainability appraisal in BIM
The provision of Application Programming Interface (API) in BIM-enable tools can contribute to facilitating BIM-related research. APIs are useful links for running plug-ins and external programmes but they are yet to be fully exploited in expanding the BIM scope. The modelling of n-Dimensional (nD) building performance measures can potentially benefit from BIM extension through API implementations. Sustainability is one such measure associated with buildings. For the structural engineer, recent design criteria have put great emphasis on the sustainability credentials as part of the traditional criteria of structural integrity, constructability and cost. This paper examines the utilization of API in BIM extension and presents a demonstration of an API application to embed sustainability issues into the appraisal process of structural conceptual design options in BIM. It concludes that API implementations are useful in expanding the BIM scope. Also, the approach including process modelling, algorithms and object-based instantiations demonstrated in the API implementation can be applicable to other nD building performance measures as may be relevant to the various professional platforms in the construction domain
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