307 research outputs found

    Sustainable high quality recycling of aggregates from waste-to-energy, treated in a wet bottom ash processing installation, for use in concrete products

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    Nowadays, more efforts towards sustainability are required from the concrete industry. Replacing traditional aggregates by recycled bottom ash (BA) from municipal solid waste incineration can contribute to this goal. Until now, only partial replacement has been considered to keep the concrete workability, strength and durability under control. In this research, the feasibility of a full aggregate replacement was investigated for producing prefabricated Lego bricks. It was found that the required compressive strength class for this purpose (C20/25) could be achieved. Nevertheless, a thorough understanding of the BA properties is needed to overcome other issues. As BA is highly absorptive, the concrete's water demand is high. This workability issue can be dealt with by subjecting the fine BA fraction to a crushing operation to eliminate the porous elements and by pre-wetting the fine and coarse BA fractions in a controlled manner. In addition, a reactive NaOH washing is needed to avoid formation of longitudinal voids and the resulting expansion due to the metallic aluminum present in the BA. Regarding the long-term behavior, heavy metal leaching and freeze-thaw exposure are not problematic, though there is susceptibility to acetic and lactic acid attack and maybe increased sensitivity to alkali-silica reaction

    Joint cosmological and gravitational-wave population inference using dark sirens and galaxy catalogues

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    In the absence of numerous gravitational-wave detections with confirmed electromagnetic counterparts, the "dark siren" method has emerged as a leading technique of gravitational-wave cosmology. The method allows redshift information of such events to be inferred statistically from a catalogue of potential host galaxies. Due to selection effects, dark siren analyses necessarily depend on the mass distribution of compact objects and the evolution of their merger rate with redshift. Informative priors on these quantities will impact the inferred posterior constraints on the Hubble constant (H0H_0). It is thus crucial to vary these unknown distributions during an H0H_0 inference. This was not possible in earlier analyses due to the high computational cost, restricting them to either excluding galaxy catalogue information, or fixing the gravitational-wave population mass distribution and risking introducing bias to the H0H_0 measurement. This paper introduces a significantly enhanced version of the Python package GWCOSMO, which allows joint estimation of cosmological and compact binary population parameters. This thereby ensures the analysis is now robust to a major source of potential bias. The gravitational-wave events from the Third Gravitational-Wave Transient Catalogue are reanalysed with the GLADE+ galaxy catalogue, and an updated, more reliable measurement of H0=69−7+12H_0=69^{+12}_{-7} km s−1^{-1} Mpc−1^{-1} is found (maximum a posteriori probability and 68% highest density interval). This improved method will enable cosmological analyses with future gravitational-wave detections to make full use of the information available (both from galaxy catalogues and the compact binary population itself), leading to promising new independent bounds on the Hubble constant.Comment: 30 pages, 11 figure

    Development and validation of a high-density SNP genotyping array for African Oil Palm

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    High-density single nucleotide polymorphism (SNP) genotyping arrays are powerful tools that can measure the level of genetic polymorphism within a population. To develop a whole-genome SNP array for oil palms, SNP discovery was performed using deep resequencing of eight libraries derived from 132 Elaeis guineensis and Elaeis oleifera palms belonging to 59 origins, resulting in the discovery of >3 million putative SNPs. After SNP filtering, the Illumina OP200K custom array was built with 170 860 successful probes. Phenetic clustering analysis revealed that the array could distinguish between palms of different origins in a way consistent with pedigree records. Genome-wide linkage disequilibrium declined more slowly for the commercial populations (ranging from 120 kb at r2 = 0.43 to 146 kb at r2 = 0.50) when compared with the semi-wild populations (19.5 kb at r2 = 0.22). Genetic fixation mapping comparing the semi-wild and commercial population identified 321 selective sweeps. A genome-wide association study (GWAS) detected a significant peak on chromosome 2 associated with the polygenic component of the shell thickness trait (based on the trait shell-to-fruit; S/F %) in tenera palms. Testing of a genomic selection model on the same trait resulted in good prediction accuracy (r = 0.65) with 42% of the S/F%variation explained. The first high-density SNP genotyping array for oil palm has been developed and shown to be robust for use in genetic studies and with potential for developing early trait prediction to shorten the oil palm breeding cycle

    The predominance of Human Immunodeficiency Virus type 1 (HIV-1) circulating recombinant form 02 (CRF02_AG) in West Central Africa may be related to its replicative fitness

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    BACKGROUND: CRF02_AG is the predominant HIV strain circulating in West and West Central Africa. The aim of this study was to test whether this predominance is associated with a higher in vitro replicative fitness relative to parental subtype A and G viruses. Primary HIV-1 isolates (10 CRF02_AG, 5 subtype A and 5 subtype G) were obtained from a well-described Cameroonian cohort. Growth competition experiments were carried out at equal multiplicity of infection in activated T cells and monocyte-derived dendritic cells (MO-DC) in parallel. RESULTS: Dual infection/competition experiments in activated T cells clearly indicated that CRF02_AG isolates had a significant replication advantage over the subtype A and subtype G viruses. The higher fitness of CRF02_AG was evident for isolates from patients with CD4+ T cell counts >200 cells/μL (non-AIDS) or CD4+ T cell counts <200 cells/μL (AIDS), and was independent of the co-receptor tropism. In MO-DC cultures, CRF02_AG isolates showed a slightly but not significantly higher replication advantage compared to subtype A or G isolates. CONCLUSION: We observed a higher ex vivo replicative fitness of CRF02_AG isolates compared to subtype A and G viruses from the same geographic region and showed that this was independent of the co-receptor tropism and irrespective of high or low CD4+ T cell count. This advantage in replicative fitness may contribute to the dominant spread of CRF02_AG over A and G subtypes in West and West Central Africa

    The preclinical pharmacology of the high affinity anti-IL-6R Nanobody (R) ALX-0061 supports its clinical development in rheumatoid arthritis

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    Introduction: The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody (R) with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum albumin. We describe here the relevant aspects of its in vitro and in vivo pharmacology. Methods: ALX-0061 is composed of an affinity-matured IL-6R-targeting domain fused to an albumin-binding domain representing a minimized two-domain structure. A panel of different in vitro assays was used to characterize the biological activities of ALX-0061. The pharmacological properties of ALX-0061 were examined in cynomolgus monkeys, using plasma levels of total soluble (s)IL-6R as pharmacodynamic marker. Therapeutic effect was evaluated in a human IL-6-induced acute phase response model in the same species, and in a collagen-induced arthritis (CIA) model in rhesus monkeys, using tocilizumab as positive control. Results: ALX-0061 was designed to confer the desired pharmacological properties. A 200-fold increase of target affinity was obtained through affinity maturation of the parental domain. The high affinity for sIL-6R (0.19 pM) translated to a concentration-dependent and complete neutralization of sIL-6R in vitro. In cynomolgus monkeys, ALX-0061 showed a dose-dependent and complete inhibition of hIL-6-induced inflammatory parameters, including plasma levels of C-reactive protein (CRP), fibrinogen and platelets. An apparent plasma half-life of 6.6 days was observed after a single intravenous administration of 10 mg/kg ALX-0061 in cynomolgus monkeys, similar to the estimated expected half-life of serum albumin. ALX-0061 and tocilizumab demonstrated a marked decrease in serum CRP levels in a non-human primate CIA model. Clinical effect was confirmed in animals with active drug exposure throughout the study duration. Conclusions: ALX-0061 represents a minimized bispecific biotherapeutic of 26 kDa, nearly six times smaller than monoclonal antibodies. High in vitro affinity and potency was demonstrated. Albumin binding as a half-life extension technology resulted in describable and expected pharmacokinetics. Strong IL-6R engagement was shown to translate to in vivo effect in non-human primates, demonstrated via biomarker deregulation as well as clinical effect. Presented results on preclinical pharmacological properties of ALX-0061 are supportive of clinical development in RA
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