28 research outputs found
Bělina, Pavel: Česká města v 18. století a osvícenské reformy [Die böhmischen Städte im 18. Jahrhundert und die Reformen der Aufklärung]
Beförderer der Aufklärung in Mittel- und Osteuropa. Freimaurer, Gesellschaften, Clubs. Hrsg. v. Eva H. Balász, Ludwig Hammermayer, Hans Wojtowicz (Studien zur Geschichte der Kulturbeziehungen in Mittel- und Osteuropa 5)
Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context
Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences
have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this
paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but
also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.
Avidity engineering of human heavy-chain-only antibodies mitigates neutralization resistance of SARS-CoV-2 variants
Emerging SARS-CoV-2 variants have accrued mutations within the spike protein rendering most therapeutic monoclonal antibodies against COVID-19 ineffective. Hence there is an unmet need for broad-spectrum mAb treatments for COVID-19 that are more resistant to antigenically drifted SARS-CoV-2 variants. Here we describe the design of a biparatopic heavy-chain-only antibody consisting of six antigen binding sites recognizing two distinct epitopes in the spike protein NTD and RBD. The hexavalent antibody showed potent neutralizing activity against SARS-CoV-2 and variants of concern, including the Omicron sub-lineages BA.1, BA.2, BA.4 and BA.5, whereas the parental components had lost Omicron neutralization potency. We demonstrate that the tethered design mitigates the substantial decrease in spike trimer affinity seen for escape mutations for the hexamer components. The hexavalent antibody protected against SARS-CoV-2 infection in a hamster model. This work provides a framework for designing therapeutic antibodies to overcome antibody neutralization escape of emerging SARS-CoV-2 variants
An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants
The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity.The MANCO project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 101003651). This work made use of the Dutch national e infrastructure with the support of the SURF Cooperative using grant no. EINF-2453. This research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) - 398066876/GRK 2485/1; BMBF (Federal Ministry of Education and Research) project entitled RAPID (Risk assessment in re-pandemic respiratory infectious diseases), 01KI1723G, Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20)N
An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern
The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other Variants of Concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and/or hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs, and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.The MANCO project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101003651). This work made use of the Dutch national e-infrastructure with the support of the SURF Cooperative using grant no. EINF-2453. This research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) -398066876/GRK 2485/1; BMBF (Federal Ministry of Education and Research) project entitled RAPID (Risk assessment in re-pandemic respiratory infectious diseases), 01KI1723G, Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20)Peer reviewe
Magnetic Fields toward Ophiuchus-B Derived from SCUBA-2 Polarization Measurements
We present the results of dust emission polarization measurements of Ophiuchus-B (Oph-B) carried out using the Submillimetre Common-User Bolometer Array 2 (SCUBA-2) camera with its associated polarimeter (POL-2) on the James Clerk Maxwell Telescope in Hawaii. This work is part of the B-fields in Star-forming Region Observations survey initiated to understand the role of magnetic fields in star formation for nearby star-forming molecular clouds. We present a first look at the geometry and strength of magnetic fields in Oph-B. The field geometry is traced over ~0.2 pc, with clear detection of both of the sub-clumps of Oph-B. The field pattern appears significantly disordered in sub-clump Oph-B1. The field geometry in Oph-B2 is more ordered, with a tendency to be along the major axis of the clump, parallel to the filamentary structure within which it lies. The degree of polarization decreases systematically toward the dense core material in the two sub-clumps. The field lines in the lower density material along the periphery are smoothly joined to the large-scale magnetic fields probed by NIR polarization observations. We estimated a magnetic field strength of 630 ± 410 μG in the Oph-B2 sub-clump using a Davis–Chandrasekhar–Fermi analysis. With this magnetic field strength, we find a mass-to-flux ratio λ = 1.6 ± 1.1, which suggests that the Oph-B2 clump is slightly magnetically supercritical
JCMT BISTRO Survey: Magnetic Fields within the Hub-filament Structure in IC 5146
We present the 850 μm polarization observations toward the IC 5146 filamentary cloud taken using the Submillimetre Common-User Bolometer Array 2 (SCUBA-2) and its associated polarimeter (POL-2), mounted on the James Clerk Maxwell Telescope, as part of the B-fields In STar forming Regions Observations. This work is aimed at revealing the magnetic field morphology within a core-scale (lesssim1.0 pc) hub-filament structure (HFS) located at the end of a parsec-scale filament. To investigate whether the observed polarization traces the magnetic field in the HFS, we analyze the dependence between the observed polarization fraction and total intensity using a Bayesian approach with the polarization fraction described by the Rice likelihood function, which can correctly describe the probability density function of the observed polarization fraction for low signal-to-noise ratio data. We find a power-law dependence between the polarization fraction and total intensity with an index of 0.56 in A V ~ 20–300 mag regions, suggesting that the dust grains in these dense regions can still be aligned with magnetic fields in the IC 5146 regions. Our polarization maps reveal a curved magnetic field, possibly dragged by the contraction along the parsec-scale filament. We further obtain a magnetic field strength of 0.5 ± 0.2 mG toward the central hub using the Davis–Chandrasekhar–Fermi method, corresponding to a mass-to-flux criticality of ~1.3 ± 0.4 and an Alfvénic Mach number of <0.6. These results suggest that gravity and magnetic field are currently of comparable importance in the HFS and that turbulence is less important